ISSN: 2692-4730
Annals of Pancreatic Disorders and Treatment
Mini Review       Open Access      Peer-Reviewed

Progress in the development of vaccines for pancreatic adenocarcinoma

Mahmoud Singer1*, Ahmed M Elsayed2 and Mohamed I Husseiny3

1University of California Irvine, School of Medicine, Irvine, CA 92697, USA
2Department of Society and Genetics, College of Letters and Science, University of California, Los Angeles, California, USA
3Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA
*Corresponding author: Mahmoud Singer, University of California Irvine, School of Medicine, Irvine, CA 92697, USA, Email:,
Received: 18 March, 2023 | Accepted: 05 April, 2024 | Published: 06 April, 2024
Keywords: Salmonella-based vaccine; Vaccine design; Cancer vaccine; Pancreatic adenocarcinoma; Immunotherapy

Cite this as

Singer M, Elsayed AM, Husseiny MI (2024) Progress in the development of vaccines for pancreatic adenocarcinoma. Ann Pancreat Disord Treatm 6(1): 001-005. DOI: 10.17352/apdt.000011


© 2024 Singer M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Pancreatic cancer, which is regarded as the third deadliest cancer globally, poses a significant challenge because of its limited range of treatment options and high mortality rate. Currently, there is a focus on both the development of a novel concept in vaccine designing and the parallel study of the associated immune mechanisms. To further our understanding of the healthcare field, a variety of promising designs have been introduced for in-depth study. The designs were developed to include the mKRAS-specific amphiphile vaccine, which targets a specific mutation in the KRAS gene in addition to the multi-antigen targeted DNA vaccine, which aims to stimulate an immune response against multiple cancer antigens. Furthermore, later designs of vaccines were introduced based on the development of peptide-based cancer vaccines, mRNA-based vaccines, cell-based vaccines, and engineered bacterial vectors using an oral Salmonella-based vaccine. The study presents the concept on which the new vaccine is based and discusses the up-to-date immunological manifestations of these designed vaccines.


Pancreatic cancer has a 5-year survival rate of 5% - 8% [1] and Pancreatic Ductal Adenocarcinoma (PDAC) accounts for ~90% of fatal cases [2]. Although PDAC is the ninth most prevalent cancer, it is the fourth leading cause of cancer-related death in Western countries [3]. Even with early detection, only ~20% of individuals are suitable for surgical resection [4]. Gemcitabine and 5-fluorouracil (5-FU) are the most often used treatments with little progress in outcomes [4]. The quest to develop a vaccine for PDAC has garnered significant attention in both pre-clinical and clinical trials for a long time [1]. Upon evaluation, it is found that the tumor site does not have tumor-specific lymphocytes, which could be attributed to the tumor’s poor immunogenicity, steric hindrance of T-cell migration, and potential tolerance to the effect of the surrounding microenvironment [5,6]. An important field of study involves investigating the potential of vaccine-based treatments to promote the proliferation and stimulation of lymphocytes that specifically target pancreatic cancer. The potential failure of current cancer vaccines is disheartening, especially because of the inadequacy of antigen delivery or the activation of innate immunity [7]. Therefore, a need for a more specific neo-antigen, controlling the tumor microenvironment, and integration of innate and adaptive immune cells are the main pillars for addressing a novel and successful theory for vaccine design.

Current and future vaccine designs

mKRAS-specific amphiphile vaccine: KRAS is a gene that makes a protein called K-Ras that is part of the RAS/MAPK signaling pathway. The presence of mutations in the KRAS gene is a common characteristic (90-95%) observed in pancreatic adenocarcinomas. Among all the genes in PDAC, this one is the most mutated [8]. A clinical study was carried out to examine constitutive activation of KRAS, which usually represents more than 98% of all activating mutations, using amphiphile modification of G12D and G12R mutant KRAS (mKRAS) (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) peptides (Amph-Peptides-2P) in conjunction with CpG oligonucleotide adjuvant (Amph-CpG-7909) [9]. In his study, an essential focus is placed on the appearance of cross-reactive T-cells in non-immunizing mKRAS antigens. Furthermore, there is a notable absence of data regarding innate immunity.

Multi-antigen targeted DNA vaccine: The hypothesis of using multi-antigen is mainly based on targeting the melanoma-associated antigen type-I protein (MAGE-type I) which is well-conserved, associated with cancer, and exhibits strong immunogenicity [10]. MAGE plays a role in regulating tumor‑stromal crosstalk in PDAC and is found to be overexpressed in a chemo-resistant patient. Vaccination against multiple MAGE antigens robust a favorable immune response against the growth of gemcitabine-resistant tumors [11]. Due to the current lack of understanding of the exact mechanism of MAGE and its safety in overcoming cancer chemoresistance and progression, it is too early to plan for clinical treatment.

Peptide-based cancer vaccines: Targeting the immunosuppressive and fibrotic tumor microenvironment has recently attracted attention in the immunotherapy for PDAC by using different key molecules such as transforming growth factor-β (TGFβ) derived peptides, anti-PD-1 antibodies, anti-CSF-1R antibodies and Anti-VEGF receptor 2 [12]. The concept is originally initiated by targeting viral peptides [13]. Until now, no single immune-inhibitory checkpoint has been proven to be an effective therapy or vaccine in vivo, and none have shown long-term protection against disease recurrence. Therefore, many clinical trials are currently running with different therapeutic modalities, including immune checkpoint inhibitors, to improve clinical outcomes.

mRNA-based vaccines: The new approach of using mRNA vaccines has improved the maturity of personalized neoantigen vaccines. mRNA can be captured by antigen-presenting cells and presented via major histocompatibility complex (MHC) molecules, which leads to clonogenic immune activation and expansion [14,15]. Although the early clinical trials show promising results, several challenges, like the identification of suitable antigens and immune evasion by tumors, still need to be addressed.

Cell-based vaccines: The fusion of tumor cells and dendritic cells (DCs) triggers the activation of a diverse antitumor immune system. Vaccination with DC/tumor fusions also resulted in the proliferation of lymphocytes specific to tumor antigens and infiltrated the tumor site [7]. DC-based vaccines are very promising in establishing a personalized effective therapy because of the tumor microenvironment. However, recent clinical trials using DCs combined with immune checkpoint inhibitors are under investigation. Another method employed in cell-based research involves the use of human PDAC cell lines that have undergone genetic modification. This modification allows the cells to express αGal via retroviral transfer of the murine αGT gene. This approach is commercially referred to as Algenpantucel-L [16]. The study showed an effective result when combined with gemcitabine chemotherapy in advanced HCC.

Engineering bacterial vectors: Oral Salmonella-based vaccine. Engineering bacterial vectors to deliver tumor antigens provides an efficient way of better stimulating immune cell attack of tumor cells or suppressing the immune cells to control immune reactions [17]. Such bacterial-based therapies are in development and hold promise for hard-headed neoplasms. Bacteria have advantages, including the expression of anti-tumor proteins and the transfer of expression vectors into cancer cells. In addition, bacteria are highly mobile and actively move away from the vasculature, penetrate deeply, and accumulate in tumor tissue [18]. Other cancer treatments may not penetrate the cancer well [19]. The oral vaccine model for cancer is designed from the type III secretion system (T3SS) of Salmonella and exploited for expression of tumor antigen into the cytosol of antigen-presenting cells (APCs) to generate tumor-specific cytotoxic lymphocytes (CTLs) [20]. Afterward, APCs process and present antigens to the immune cells [21-23]. This technology is being used for the development of a vaccine for cancers [24]. The Salmonella Pathogenicity Island 2 (SPI2) system of Salmonella has been used to construct a cancer vaccine [23-25]. Herein, surviving has been used, which is known as a tumor antigen overexpressed by 70-80% of cancers and a target for cancer immunotherapy [26]. This vaccine-induced CD8 T-cell-mediated antitumor activity in overexpressed survivin mice tumor models [24,25]. Similarly, the Salmonella-based vaccine could enhance NKT activation through CD1d and TLR-mediated-DCs and induce subsequent effector responses by NKT, NK, and T-cells in colon and glioblastoma cancers [23]. Similarly to the Salmonella-based vaccine, others have used the GVAX pancreas vaccine containing Listeria monocytogenes expressing mesothelin [19]. As a superior model, Oral Salmonella could improve long-term antigen presentation with higher penetration and favorably invade tumors [27]. Engineered Salmonella was tested in pre- and clinical cancers [28-30] and in pancreatic cancer [31] and was found to be safe with no risk of lung [32] or liver damage [33].


Recently, there has been promising efficacy for PDAC with individualized neoantigen cancer vaccines. The main target for all the recent therapeutic vaccines is to generate a well-developed immune response to eradicate pancreatic adenocarcinoma. However, the immune mechanisms behind this treatment are not fully established, and no vaccine has successfully eradicated PDAC [37]. Several clinical trials with different vaccine approaches have been wrought in the hope of controlling and recovering pancreatic cancer (Table 1) [5,6,8,10]. While aiming to target cancer T-cells specifically, the effectiveness in achieving the desired goal is not fully efficient [26,30] by modulating various immune subsets, a re-formulator equation can be induced, resulting in better-enhanced tumor necrosis. Several trials were pursued to inhibit the cancer-promoting role of neutrophils [38,39]. Some studies were more developed to rationalize the neutrophil-to-lymphocyte impact on tumor progression and modulate this ratio to induce better clinical outcomes, as lower ratio value and elevated lymphocyte frequency improved the response for immunotherapy designing [40-42].

The cross-talk between fibroblast and macrophages in the tumor microenvironment is enhanced when the expression of oncoprotein p21 is elevated in tumor-associated macrophages (TAM) because of stromal interaction or chemotherapy treatment. Modulating or blocking p21 expression levels in TAMs was found to be an effective strategy in suppressing tumor progression [38]. This cross-talk is also believed to involve efferocytosis-associated genes, which have been implicated in promoting tumor metastasis [39]. It is worthy to mention that NK cells are acquiring a greater understanding of their role in combinatorial immunotherapy using gemcitabine and NK immunotherapy [43], or combinatorial using NK cells and chemotherapy [44]. The interaction between NK cells and the conditions of the tumor microenvironment controls the fate of the therapy in pancreatic cancers [45]. When considering this perspective, it becomes clear that the immune profiling surrounding the tumor and the combination formula play a crucial role in determining tumor regression or progression.


Developing novel therapies for pancreatic adenocarcinoma poses a significant challenge due to the various approaches required. There is a high demand for a vaccine that can serve as a prophylactic, protective, and therapeutic measure. By delving into the intricate workings of the immune system and exploring the potential of combining different vaccine components, we can pave the way for the development of a highly efficacious, long-lasting vaccine.

  1. Van Laethem JL, Verslype C, Iovanna JL, Michl P, Conroy T, Louvet C, Hammel P, Mitry E, Ducreux M, Maraculla T, Uhl W, Van Tienhoven G, Bachet JB, Maréchal R, Hendlisz A, Bali M, Demetter P, Ulrich F, Aust D, Luttges J, Peeters M, Mauer M, Roth A, Neoptolemos JP, Lutz M. New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel. Ann Oncol. 2012 Mar;23(3):570-576. doi: 10.1093/annonc/mdr351. Epub 2011 Aug 1. PMID: 21810728.
  2. Gunderson AJ, Yamazaki T, McCarty K, Phillips M, Alice A, Bambina S, Zebertavage L, Friedman D, Cottam B, Newell P, Gough MJ, Crittenden MR, Van der Veken P, Young KH. Blockade of fibroblast activation protein in combination with radiation treatment in murine models of pancreatic adenocarcinoma. PLoS One. 2019 Feb 6;14(2):e0211117. doi: 10.1371/journal.pone.0211117. PMID: 30726287; PMCID: PMC6364920.
  3. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12. Erratum in: CA Cancer J Clin. 2021 Jul;71(4):359. PMID: 33433946.
  4. Karanikas M, Esempidis A, Chasan ZT, Deftereou T, Antonopoulou M, Bozali F. Pancreatic Cancer from Molecular Pathways to Treatment Opinion. J Cancer. 2016; 7:1328-39.
  5. Sahin IH, Askan G, Hu ZI, O'Reilly EM. Immunotherapy in pancreatic ductal adenocarcinoma: an emerging entity? Ann Oncol. 2017 Dec 1;28(12):2950-2961. doi: 10.1093/annonc/mdx503. PMID: 28945842; PMCID: PMC5834032.
  6. Feng M, Xiong G, Cao Z, Yang G, Zheng S, Song X, You L, Zheng L, Zhang T, Zhao Y. PD-1/PD-L1 and immunotherapy for pancreatic cancer. Cancer Lett. 2017 Oct 28;407:57-65. doi: 10.1016/j.canlet.2017.08.006. Epub 2017 Aug 18. PMID: 28826722.
  7. Orr S, Huang L, Moser J, Stroopinsky D, Gandarilla O, DeCicco C, Liegel J, Tacettin C, Ephraim A, Cheloni G, Torres D, Kufe D, Rosenblatt J, Hidalgo M, Muthuswamy SK, Avigan D. Personalized tumor vaccine for pancreatic cancer. Cancer Immunol Immunother. 2023 Feb;72(2):301-313. doi: 10.1007/s00262-022-03237-x. Epub 2022 Jul 14. PMID: 35834008.
  8. Amintas S, Fernandez B, Chauvet A, Chiche L, Laurent C, Belleannée G, Marty M, Buscail E, Dabernat S. KRAS gene mutation quantification in the resection or venous margins of pancreatic ductal adenocarcinoma is not predictive of disease recurrence. Sci Rep. 2022 Feb 22;12(1):2976. doi: 10.1038/s41598-022-07004-x. PMID: 35194118; PMCID: PMC8864048.
  9. Pant S, Wainberg ZA, Weekes CD, Furqan M, Kasi PM, Devoe CE, Leal AD, Chung V, Basturk O, VanWyk H, Tavares AM, Seenappa LM, Perry JR, Kheoh T, McNeil LK, Welkowsky E, DeMuth PC, Haqq CM, O'Reilly EM. Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nat Med. 2024 Feb;30(2):531-542. doi: 10.1038/s41591-023-02760-3. Epub 2024 Jan 9. PMID: 38195752; PMCID: PMC10878978.
  10. Duperret EK, Liu S, Paik M, Trautz A, Stoltz R, Liu X, Ze K, Perales-Puchalt A, Reed C, Yan J, Xu X, Weiner DB. A Designer Cross-reactive DNA Immunotherapeutic Vaccine that Targets Multiple MAGE-A Family Members Simultaneously for Cancer Therapy. Clin Cancer Res. 2018 Dec 1;24(23):6015-6027. doi: 10.1158/1078-0432.CCR-18-1013. Epub 2018 Sep 27. PMID: 30262507; PMCID: PMC6319943.
  11. Qin H, Chen J, Bouchekioua-Bouzaghou K, Meng YM, Griera JB, Jiang X, Kong X, Wang M, Xu Q, Wong PP. Immunization with a multi-antigen targeted DNA vaccine eliminates chemoresistant pancreatic cancer by disrupting tumor-stromal cell crosstalk. J Transl Med. 2023 Oct 9;21(1):702. doi: 10.1186/s12967-023-04519-3. PMID: 37814317; PMCID: PMC10561406.
  12. Perez-Penco M, Weis-Banke SE, Schina A, Siersbæk M, Hübbe ML, Jørgensen MA, Lecoq I, Lara de la Torre L, Bendtsen SK, Martinenaite E, Holmström MO, Madsen DH, Donia M, Ødum N, Grøntved L, Andersen MH. TGFβ-derived immune modulatory vaccine: targeting the immunosuppressive and fibrotic tumor microenvironment in a murine model of pancreatic cancer. J Immunother Cancer. 2022 Dec;10(12):e005491. doi: 10.1136/jitc-2022-005491. PMID: 36600556; PMCID: PMC9730419.
  13. Dhanushkodi NR, Prakash S, Quadiri A, Zayou L, Singer M, Takashi N, Vahed H, BenMohamed L. High Frequencies of Antiviral Effector Memory TEM Cells and Memory B Cells Mobilized into Herpes Infected Vaginal Mucosa Associated With Protection Against Genital Herpes. bioRxiv [Preprint]. 2023 May 24:2023.05.23.542021. doi: 10.1101/2023.05.23.542021. PMID: 37292784; PMCID: PMC10245907.
  14. Kang N, Zhang S, Wang Y. A personalized mRNA vaccine has exhibited potential in the treatment of pancreatic cancer. Holist Integr Oncol. 2023;2(1):18. doi: 10.1007/s44178-023-00042-z. Epub 2023 Jun 8. PMID: 37323470; PMCID: PMC10248956.
  15. Huang X, Zhang G, Tang TY, Gao X, Liang TB. Personalized pancreatic cancer therapy: from the perspective of mRNA vaccine. Mil Med Res. 2022 Oct 13;9(1):53. doi: 10.1186/s40779-022-00416-w. PMID: 36224645; PMCID: PMC9556149.
  16. Rouanet M, Lebrin M, Gross F, Bournet B, Cordelier P, Buscail L. Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes. Int J Mol Sci. 2017 Jun 8;18(6):1231. doi: 10.3390/ijms18061231. PMID: 28594388; PMCID: PMC5486054.
  17. Cobb J, Rawson J, Gonzalez N, Singer M, Kandeel F, Husseiny MI. Mechanism of Action of Oral Salmonella-Based Vaccine to Prevent and Reverse Type 1 Diabetes in NOD Mice. Vaccines (Basel). 2024 Mar 6;12(3):276. doi: 10.3390/vaccines12030276. PMID: 38543910; PMCID: PMC10975319.
  18. Ganai S, Arenas RB, Sauer JP, Bentley B, Forbes NS. In tumors Salmonella migrate away from vasculature toward the transition zone and induce apoptosis. Cancer Gene Ther. 2011 Jul;18(7):457-66. doi: 10.1038/cgt.2011.10. Epub 2011 Mar 25. PMID: 21436868; PMCID: PMC3117926.
  19. Lutz ER, Wu AA, Bigelow E, Sharma R, Mo G, Soares K, Solt S, Dorman A, Wamwea A, Yager A, Laheru D, Wolfgang CL, Wang J, Hruban RH, Anders RA, Jaffee EM, Zheng L. Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res. 2014 Jul;2(7):616-31. doi: 10.1158/2326-6066.CIR-14-0027. Epub 2014 Jun 18. PMID: 24942756; PMCID: PMC4082460.
  20. Xu X, Hegazy WA, Guo L, Gao X, Courtney AN, Kurbanov S, Liu D, Tian G, Manuel ER, Diamond DJ, Hensel M, Metelitsa LS. Effective cancer vaccine platform based on attenuated Salmonella and a type III secretion system. Cancer Res. 2014 Nov 1;74(21):6260-70. doi: 10.1158/0008-5472.CAN-14-1169. Epub 2014 Sep 11. PMID: 25213323; PMCID: PMC4216746.
  21. Husseiny MI, Hensel M. Construction of highly attenuated Salmonella enterica serovar Typhimurium live vectors for delivering heterologous antigens by chromosomal integration. Microbiol Res. 2008;163(6):605-15. doi: 10.1016/j.micres.2006.10.003. PMID: 19216101.
  22. Husseiny MI, Hensel M. Evaluation of Salmonella live vaccines with chromosomal expression cassettes for translocated fusion proteins. Vaccine. 2009 Jun 8;27(28):3780-7. doi: 10.1016/j.vaccine.2009.03.053. Epub 2009 Apr 8. PMID: 19464562.
  23. Husseiny MI, Wartha F, Hensel M. Recombinant vaccines based on translocated effector proteins of Salmonella Pathogenicity Island 2. Vaccine. 2007 Jan 2;25(1):185-93. doi: 10.1016/j.vaccine.2005.11.020. Epub 2005 Nov 22. PMID: 16887239.
  24. Xiong G, Husseiny MI, Song L, Erdreich-Epstein A, Shackleford GM, Seeger RC, Jäckel D, Hensel M, Metelitsa LS. Novel cancer vaccine based on genes of Salmonella pathogenicity island 2. Int J Cancer. 2010 Jun 1;126(11):2622-34. doi: 10.1002/ijc.24957. PMID: 19824039; PMCID: PMC2993175.
  25. Xu X, Husseiny MI, Goldwich A, Hensel M. Efficacy of intracellular activated promoters for generation of Salmonella-based vaccines. Infect Immun. 2010 Nov;78(11):4828-38. doi: 10.1128/IAI.00298-10. Epub 2010 Aug 23. PMID: 20732994; PMCID: PMC2976355.
  26. Arber C, Feng X, Abhyankar H, Romero E, Wu MF, Heslop HE, Barth P, Dotti G, Savoldo B. Survivin-specific T cell receptor targets tumor but not T cells. J Clin Invest. 2015 Jan;125(1):157-68. doi: 10.1172/JCI75876. Epub 2014 Nov 21. PMID: 25415440; PMCID: PMC4382259.
  27. Kasinskas RW, Forbes NS. Salmonella typhimurium specifically chemotax and proliferate in heterogeneous tumor tissue in vitro. Biotechnol Bioeng. 2006 Jul 5;94(4):710-21. doi: 10.1002/bit.20883. PMID: 16470601.
  28. Vassaux G, Nitcheu J, Jezzard S, Lemoine NR. Bacterial gene therapy strategies. J Pathol. 2006 Jan;208(2):290-8. doi: 10.1002/path.1865. PMID: 16362987.
  29. Chorobik P, Czaplicki D, Ossysek K, Bereta J. Salmonella and cancer: from pathogens to therapeutics. Acta Biochim Pol. 2013;60(3):285-97. Epub 2013 Jul 5. PMID: 23828775.
  30. Chen G, Wei DP, Jia LJ, Tang B, Shu L, Zhang K, Xu Y, Gao J, Huang XF, Jiang WH, Hu QG, Huang Y, Wu Q, Sun ZH, Zhang JF, Hua ZC. Oral delivery of tumor-targeting Salmonella exhibits promising therapeutic efficacy and low toxicity. Cancer Sci. 2009 Dec;100(12):2437-43. doi: 10.1111/j.1349-7006.2009.01337.x. Epub 2009 Sep 1. PMID: 19793349.
  31. Schmitz-Winnenthal FH, Hohmann N, Niethammer AG, Friedrich T, Lubenau H, Springer M, Breiner KM, Mikus G, Weitz J, Ulrich A, Buechler MW, Pianka F, Klaiber U, Diener M, Leowardi C, Schimmack S, Sisic L, Keller AV, Koc R, Springfeld C, Knebel P, Schmidt T, Ge Y, Bucur M, Stamova S, Podola L, Haefeli WE, Grenacher L, Beckhove P. Anti-angiogenic activity of VXM01, an oral T-cell vaccine against VEGF receptor 2, in patients with advanced pancreatic cancer: A randomized, placebo-controlled, phase 1 trial. Oncoimmunology. 2015 Mar 16;4(4):e1001217. doi: 10.1080/2162402X.2014.1001217. PMID: 26137397; PMCID: PMC4485742.
  32. Tseng CT, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, Atmar RL, Peters CJ, Couch RB. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012;7(4):e35421. doi: 10.1371/journal.pone.0035421. Epub 2012 Apr 20. Erratum in: PLoS One. 2012;7(8). doi:10.1371/annotation/2965cfae-b77d-4014-8b7b-236e01a35492. PMID: 22536382; PMCID: PMC3335060.
  33. Weingartl H, Czub M, Czub S, Neufeld J, Marszal P, Gren J, Smith G, Jones S, Proulx R, Deschambault Y, Grudeski E, Andonov A, He R, Li Y, Copps J, Grolla A, Dick D, Berry J, Ganske S, Manning L, Cao J. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol. 2004 Nov;78(22):12672-6. doi: 10.1128/JVI.78.22.12672-12676.2004. PMID: 15507655; PMCID: PMC525089.
  34. Chen Z, Zhang S, Han N, Jiang J, Xu Y, Ma D, Lu L, Guo X, Qiu M, Huang Q, Wang H, Mo F, Chen S, Yang L. A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment. Front Immunol. 2021 Aug 13;12:691605. doi: 10.3389/fimmu.2021.691605. PMID: 34484187; PMCID: PMC8414362.
  35. Hardacre JM, Mulcahy M, Small W, Talamonti M, Obel J, Krishnamurthi S, Rocha-Lima CS, Safran H, Lenz HJ, Chiorean EG. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J Gastrointest Surg. 2013 Jan;17(1):94-100; discussion p. 100-1. doi: 10.1007/s11605-012-2064-6. Epub 2012 Nov 15. PMID: 23229886.
  36. Bassani-Sternberg M, Digklia A, Huber F, Wagner D, Sempoux C, Stevenson BJ, Thierry AC, Michaux J, Pak H, Racle J, Boudousquie C, Balint K, Coukos G, Gfeller D, Martin Lluesma S, Harari A, Demartines N, Kandalaft LE. A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients. Front Immunol. 2019 Aug 8;10:1832. doi: 10.3389/fimmu.2019.01832. PMID: 31440238; PMCID: PMC6694698.
  37. Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, Lihm J, Ceglia N, Guasp P, Chu A, Yu R, Chandra AK, Waters T, Ruan J, Amisaki M, Zebboudj A, Odgerel Z, Payne G, Derhovanessian E, Müller F, Rhee I, Yadav M, Dobrin A, Sadelain M, Łuksza M, Cohen N, Tang L, Basturk O, Gönen M, Katz S, Do RK, Epstein AS, Momtaz P, Park W, Sugarman R, Varghese AM, Won E, Desai A, Wei AC, D'Angelica MI, Kingham TP, Mellman I, Merghoub T, Wolchok JD, Sahin U, Türeci Ö, Greenbaum BD, Jarnagin WR, Drebin J, O'Reilly EM, Balachandran VP. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023 Jun;618(7963):144-150. doi: 10.1038/s41586-023-06063-y. Epub 2023 May 10. PMID: 37165196; PMCID: PMC10171177.
  38. Henderson EA, Ivey A, Choi SJ, Santiago S, McNitt D, Liu TW, et al. Group A streptococcal collagen-like protein 1 restricts tumor growth in murine pancreatic adenocarcinoma and inhibits cancer-promoting neutrophil extracellular traps. Front Immunol. 2024;15:1363962.
  39. Varzaru B, Iacob RA, Bunduc S, Manea I, Sorop A, Spiridon A, Chelaru R, Croitoru A, Topala M, Becheanu G, Dumbrava M, Dima S, Popescu I, Gheorghe C. Prognostic Value of Circulating Cell-Free DNA Concentration and Neutrophil-to-Lymphocyte Ratio in Patients with Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study. Int J Mol Sci. 2024 Mar 1;25(5):2854. doi: 10.3390/ijms25052854. PMID: 38474101; PMCID: PMC10931924.
  40. Merlo I, Ardiles V, Sanchez-Clariá R, Fratantoni E, de Santibañes E, Pekolj J, Mazza O, de Santibañes M. Prognostic Factors in Resected Pancreatic Ductal Adenocarcinoma: Is Neutrophil-Lymphocyte Ratio a Useful Marker? J Gastrointest Cancer. 2023 Jun;54(2):580-588. doi: 10.1007/s12029-022-00839-7. Epub 2022 Jun 2. PMID: 35653056.
  41. Reddy AV, Hill CS, Sehgal S, Zheng L, He J, Laheru DA, Jesus-Acosta A, Herman JM, Meyer J, Narang AK. Post-radiation neutrophil-to-lymphocyte ratio is a prognostic marker in patients with localized pancreatic adenocarcinoma treated with anti-PD-1 antibody and stereotactic body radiation therapy. Radiat Oncol J. 2022 Jun;40(2):111-119. doi: 10.3857/roj.2021.01060. Epub 2022 May 20. PMID: 35796114; PMCID: PMC9262702.
  42. Romano L, Giuliani A, Tomarelli C, Nervini A, Lazzarin G, Pessia B, Vicentini V, Carlei F, Schietroma M. Impact of Preoperative Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios on Long-Term Survival in Patients with Operable Pancreatic Ductal Adenocarcinoma. Med Princ Pract. 2022;31(6):586-594. doi: 10.1159/000527360. Epub 2022 Nov 2. PMID: 36323225; PMCID: PMC9841763.
  43. Koh EK, Lee HR, Son WC, Park GY, Kim J, Bae JH, Park YS. Combinatorial immunotherapy with gemcitabine and ex vivo-expanded NK cells induces anti-tumor effects in pancreatic cancer. Sci Rep. 2023 May 11;13(1):7656. doi: 10.1038/s41598-023-34827-z. PMID: 37169953; PMCID: PMC10175562.
  44. Yang X, Li C, Yang H, Li T, Ling S, Zhang Y, Wu F, Liu X, Liu S, Fan C, Wang Q. Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer. Nano Lett. 2024 Mar 20;24(11):3421-3431. doi: 10.1021/acs.nanolett.4c00002. Epub 2024 Feb 20. PMID: 38377170.
  45. Fiore PF, Di Pace AL, Conti LA, Tumino N, Besi F, Scaglione S, Munari E, Moretta L, Vacca P. Different effects of NK cells and NK-derived soluble factors on cell lines derived from primary or metastatic pancreatic cancers. Cancer Immunol Immunother. 2023 Jun;72(6):1417-1428. doi: 10.1007/s00262-022-03340-z. Epub 2022 Nov 30. PMID: 36451048; PMCID: PMC10198856.

Help ?