Vaccines for the treatment of malignant neoplasms

Abstract

Malignant cells capable to form tumors arise as a result of mutations in the genes of somatic cells. Mutant proteins, mutated gene products and impaired expression of non-mutated genes make malignant cells distinct from other cells in the body. Immune system is able to recognize these differences. Appropriate immune response against altered antigens allows the organism to prevent the development of malignant neoplasms. When a tumor in an individual has arisen and develops, it remains possible to induce immune response against malignant cells and thus stop or slow down the progression of cancer, in some cases it is even possible to achieve a complete recovery of the patient.

Therapeutic antitumor vaccination is a method of immunotherapy of cancer patients, that targets an induction of adaptive immune responses specific to tumor antigens. Recent advances in the field of immunology and genetics of tumors allow for a comprehensive analysis of the multitude of tumor antigens of a particular patient, to select the best immunogenic epitopes for this patient, which contributes to significant progress in the development of therapeutic antitumor vaccines. This review considers the main approaches in the development of therapeutic antitumor vaccines, which are currently at different stages and demonstrate significantly different clinical efficacy.

Keywords:tumor; vaccine; antigen; tumor-associated antigens; neoantigens; review

Received 11.06.2019 Accepted 16.06.2019

For citation: Lebedeva E.S., Ataullakhanov R.I., Khaitov R.M. Vaccines for the treatment of malignant neoplasms. Immunologiya. 2019; 40 (4): doi: 10.24411/0206-4952-2019-14008.

Acknowledgments. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

References

1. Foley E.J. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953; 13: 835-7.

2. Dunn G.P., Bruce A.T., Ikeda H., Old L.J., et al. Cancer immunoediting : from immuno- surveillance to tumor escape. Nat. Immunol. 2002; 3: 991-8. doi: 10.1038/ni1102-991.

3. Nemunaitis J. Vaccines in cancer : GVAX® , a GM-CSF gene vaccine. Expert Rev. Vaccines. 2005; 4: 259-74. doi: 10.1586/14760584.4.3.259.

4. Vuky J., Corman J.M., Porter C., Olgac S., et al. Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer. Oncologist. 2013; 18: 687-8. doi: 10.1634/theoncologist.2011-0234.

5. Santegoets S.J., Stam A.G., Lougheed S.M., Gall H., et al. T cell profiling reveals high CD4+CTLA-4+ T cell frequency as dominant predictor for survival after Prostate GVAX/ipilimumab treatment. Cancer Immunol. Immunother. 2013; 62: 245-56. doi: 10.1007/s00262-012-1330-5.

6. Nemunaitis J., Jahan T., Ross H., Sterman D., et al. Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in advanced-stage non-small-cell lung cancer. Cancer Gene Ther. 2006; 13: 555-62. doi: 10.1038/sj.cgt.7700922.

7. Lipson E.J., Sharfman W.H., Chen S., McMiller T.L., et al. Safety and immunologic correlates of Melanoma GVAX, a GM-CSF secreting allogeneic melanoma cell vaccine administered in the adjuvant setting. J. Transl. Med. 2015; 13: 214. doi: 10.1186/s12967-015-0572-3.

8. Zheng L., Edil B.H., Soares K.C., El-Shami K., et al. A safety and feasibility study of an allogeneic colon cancer cell vaccine administered with a granulocyte-macrophage colony stimulating factor-producing bystander cell line in patients with metastatic colorectal cancer. Ann. Surg. Oncol. 2014; 21: 3931-7. doi: 10.1245/s10434-014-3844-x.

9. Yarchoan M., Ferguson A.K., Durham J.N., Rozich N., et al. A phase II study of GVAX colon vaccine with cyclophosphamide and pembrolizumab in patients with mismatch repair-proficient (MMR-p) advanced colorectal cancer. J. Clin. Oncol. 2019; 37 (4 suppl.): 563. doi: 10.1200/JCO.2019.37.4_suppl.563.

10. Le D.T., Wang-Gillam A., Picozzi V., Greten T.F, et al. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J. Clin. Oncol. 2015; 33: 1325-33. doi: 10.1200/JCO.2014.57.4244.

11. Le D.T., Ko A.H., Wainberg Z.A., Picozzi V.J., et al. Results from a phase 2b, randomized, multicenter study of GVAX pancreas and CRS-207 compared to chemotherapy in adults with previously-treated metastatic pancreatic adenocarcinoma (ECLIPSE Study). J. Clin. Oncol. 2017; 35 (4 suppl.): 345. doi: 10.1200/JCO.2017.35.4_suppl.345.

12. Qin L., Smith B.D., Tsai H.L., Yaghi N.K., et al. Induction of high-titer IgG antibodies against multiple leukemia-associated antigens in CML patients with clinical responses to K562/GVAX immunotherapy. Blood Cancer J. 2013; 3: e145. doi: 10.1038/bcj.2013.44.

13. Hardacre J.M., Mulcahy M., Small W., Talamonti M., et al. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: a phase 2 study. J. Gastrointest. Surg. 2013; 17: 94-100. doi: 10.1007/s11605-012-2064-6.

14. Moiseyenko V.M., Danilov A.O., Baldueva I.A., Danilova A.B., et al. Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors Ann. Oncol. 2005; 16: 162-8. doi: 10.1093/annonc/mdi028.

15. Podrazil M., Horvath R., Becht E., Rozkova D., et al. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2015; 6: 18 192-205. doi: 10.18632/oncotarget.4145.

16. Fucikova J., Podrazil M., Jarolim L., Bilkova P., et al. Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer. Cancer Immunol. Immunother. 2018; 67:89-100. doi: 10.1007/s00262-017-2068-x.

17. Nemunaitis J., Nemunaitis M., Senzer N., Snitz P., et al. Phase II trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther. 2009; 16: 620-4. doi: 10.1038/cgt.2009.15.

18. Nemunaitis J., Dillman R.O., Schwarzenberger P.O., Senzer N., et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J. Clin. Oncol. 2006; 24: 4721-30. doi: 10.1200/JCO.2005.05.5335.

19. Giaccone G., Bazhenova L.A., Nemunaitis J., Tan M., et al. A phase III study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer. Eur. J. Cancer. 2015; 51: 2321-9. doi: 10.1016/j.ejca.2015.07.035.

20. Hsueh E.C., Morton D.L. Antigen-based immunotherapy of melanoma: Canvaxin therapeutic polyvalent cancer vaccine. Semin. Cancer Biol. 2003; 13: 401-7. doi: 10.1016/j.semcancer.2003.09.003.

21. Hsueh E.C., Nathanson L., Foshag L.J., Essner R., et al. Active specific immunotherapy with polyvalent melanoma cell vaccine for patients with in-transit melanoma metastases. Cancer. 1999; 85: 2160-9.

22. Morton D.L., Hsueh E.C., Essner R., Foshag L.J., et al. Prolonged survival of patients receiving active immunotherapy with Canvaxin therapeutic polyvalent vaccine after complete resection of melanoma metastatic to regional lymph nodes. Ann. Surg. 2002; 236: 438-48. doi: 10.1097/00000658-200210000-00006

23. DiFronzo L.A., Gupta R.K, Essner R., Foshag L.J., et al. Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J. Clin. Oncol. 2002; 20: 3242-8. doi: 10.1200/JCO.2002.01.065.

24. Hsueh E.C., Gupta R.K., Qi K, Morton D.L. Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine. J. Clin. Oncol. 1998; 16: 2913-20. doi: 10.1200/JCO.1998.16.9.2913.

25. Hoshimoto S., Faries M.B., Morton D.L., Shingai T., et al. Assessment of prognostic circulating tumor cells in a phase III trial of adjuvant immunotherapy after complete resection of stage IV melanoma. Ann. Surg. 2012; 255: 357-62. doi: 10.1097/SLA.0b013e3182380f56.

26. Faries M.B., Mozzillo N., Kashani-Sabet M., Thompson J.F., et al. Long-term survival after complete surgical resection and adjuvant immunotherapy for distant melanoma metastases. Ann. Surg. Oncol. 2017; 24: 3991-4000. doi: 10.1245/s10434-017-6072-3.

27. Tarakanovskaya M.G., Chinburen J., Batchuluun P., Munkhzaya C., et al. Open-label Phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L. J. Hepatocell. Carcinoma. 2017; 4: 59-69. doi: 10.2147/JHC.S122507.

28. Peoples G.E., Holmes J.P., Hueman M.T., Mittendorf E.A., et al. Combined clinical trial results of a HER2/neu (E75) vaccine for the prevention of recurrence in high-risk breast cancer patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin/ Cancer Res. 2008; 14: 797-803. doi: 10.1158/1078-0432.CCR-07-1448.

29. Anassi E., Ndefo U.A. Sipuleucel-T (provenge) injection: the first immunotherapy agent (vaccine) for hormone-refractory prostate cancer. P T. 2011; 36: 197-202.

30. GuhaThakurta D., Sheikh N.A., Fan L.Q., Kandadi H., et al. Humoral immune response against nontargeted tumor antigens after treatment with sipuleucel-T and its association with improved clinical outcome. Clin Cancer Res. 2015; 21: 3619-30. doi: 10.1158/1078-0432.CCR-14-2334.

31. Oudard S,. Rixe O., Beuselinck B., Linassier C., et al. A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings. Cancer Immunol. Immunother. 2011; 60: 261-71. doi: 10.1007/s00262-010-0935-9.

32. Quoix E., Lena H., Losonczy G., Forget F., et al. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet Oncol. 2016; 17: 212-23. doi: 10.1016/S1470-2045(15)00483-0.

33. Tosch C., Bastien B., Barraud L., Grellier B., et al. Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC. J. Immunother. Cancer. 2017; 5: 70. doi: 10.1186/s40425-017-0274-x.

34. Walter S., Weinschenk T., Stenzl A., Zdrojowy R., et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012; 18: 1254-61. doi: 10.1038/nm.2883.

35. Eton O., Ross M.I., East M.J., Mansfield P.F., et al. Autologous tumor-derived heat-shock protein peptide complex-96 (HSPPC-96) in patients with metastatic melanoma. J. Transl. Med. 2010; 8: 9. doi: 10.1186/1479-5876-8-9.

36. Wood C., Srivastava P., Bukowski R., Lacombe L., et al. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet. 2008; 372: 145-54. doi: 10.1016/S0140-6736(08)60697-2.

37. Belli F., Testori A., Rivoltini L., Maio M., et al. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. J. Clin. Oncol. 2002; 20: 4169-80. doi: 10.1200/JCO.2002.09.134.

38. Itoh K., Yamada A., Mine T., Noguchi M.. Recent advances in cancer vaccines: an overview. Jpn. J. Clin. Oncol. 2009; 39: 73-80. doi: 10.1093/jjco/hyn132.

39. Rosalia R.A., Quakkelaar E.D., Redeker A., Khan S., et al. Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation. Eur. J. Immunol. 2013; 43: 2554-65. doi: 10.1002/eji.201343324.

40. Kenter G.G., Welters M.J.P., Valentijn A.R.P.M., Lowik M.J.G., et al. Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N. Engl. J. Med. 2009; 361: 1838-47. doi: 10.1056/NEJMoa0810097.

41. van Poelgeest M.I.E., Welters M.J.P., Vermeij R., Stynenbosch L.F.M., et al. Vaccination against oncoproteins of HPV16 for noninvasive vulvar/vaginal lesions: lesion clearance is related to the strength of the T-cell response. Clin. Cancer Res. 2016; 22: 2342-50. doi: 10.1158/1078-0432.CCR-15-2594.

42. Kenter G.G., Welters M.J.P., Valentijn A.R.P.M., Lowik M.J.G., et al. Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity. Clin. Cancer Res. 2008; 14: 169-77. doi: 10.1158/1078-0432.CCR-07-1881.

43. van Poelgeest M.I.E., Welters M.J.P., van Esch E.M.G., Stynenbosch L.F.M., et al. HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial. J. Transl. Med. 2013; 11: 88. doi: 10.1186/1479-5876-11-88.

44. Diamandis E.P., Bast R.C., Gold P., Chu T.M., et al. Reflection on the discovery of carcinoembryonic antigen, prostate-specific antigen, and cancer antigens CA125 and CA19-9. Clin. Chem. 2013; 59: 22-31. doi: 10.1373/clinchem.2012.187047.

45. Diaz C.M., Chiappori A., Aurisicchio L., Bagchi A., et al. Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors. J. Transl. Med. 2013; 11: 62. doi: 10.1186/1479-5876-11-62.

46. Madan R.A., Arlen P.M., Gulley J.L. PANVACTM-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert Opin. Biol. Ther. 2007; 7: 543-54. doi: 10.1517/14712598.7.4.543.

47. Geynisman D.M., Zha Y., Kunnavakkam R., Aklilu M., et al. A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine in patients with pancreatic adenocarcinoma. J. Immunother. cancer. 2013; 1: 8. doi: 10.1186/2051-1426-1-8.

48. Weihrauch M.R., Ansén S., Jurkiewicz E., Geisen C., et al. Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. Clin. Cancer Res. 2005; 11: 5993-6001. doi: 10.1158/1078-0432.CCR-05-0018.

49. Morse M.A., Clay T.M., Hobeika A.C., Osada T., et al. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin. Cancer Res. 2005; 11: 3017-24. doi: 10.1158/1078-0432.CCR-04-2172.

50. Hunyadi J., András C., Szabó I., Szántó J., et al. Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer-A phase I-II study. Pathol. Oncol. Res. 2014; 20: 357-65. doi: 10.1007/s12253-013-9704-3.

51. Bilusic M., Heery C.R., Arlen P.M., Rauckhorst M., et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol. Immunother. 2014; 63: 225-34. doi: 10.1007/s00262-013-1505-8.

52. Castle J.C., Kreiter S., Diekmann J., Lower M., et al. Exploiting the mutanome for tumor vaccination. Cancer Res. 2012; 72: 1081-91. doi: 10.1158/0008-5472.CAN-11-3722.

53. Gubin M.M., Zhang X., Schuster H., Caron E., et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014; 515: 577-81. doi: 10.1038/nature13988.

54. Yadav M., Jhunjhunwala S., Phung Q.T., Lupardus P., et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature. 2014; 515: 572-6. doi: 10.1038/nature14001.

55. Sahin U., Derhovanessian E., Miller M., Kloke B.P., et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017; 547: 222-6. doi: 10.1038/nature23003.

56. Ott P.A., Hu Z., Keskin D.B., Shukla S.A., et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017; 547: 217-21. doi: 10.1038/nature22991.

57. Keskin D.B., Anandappa A.J., Sun J., Tirosh I., et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2019; 565: 234-9. doi: 10.1038/s41586-018-0792-9.

58. Ott P.A., Govindan R., Naing A., Friedlander T.W., et al. A personal neoantigen vaccine, NEO-PV-01, with anti-PD1 induces broad de novo anti-tumor immunity in patients with metastatic melanoma, NSCLC, and bladder cancer. Ann. Oncol. 2018; 29 (suppl. 8): viii400-41. doi: 10.1093/annonc/mdy288.

59. Hilf N., Kuttruff-Coqui S., Frenzel K., Bukur V., et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature. 2019; 565: 240-5. doi: 10.1038/s41586-018-0810-y.

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