The rationale for prophylactic cancer vaccines and need for a paradigm shift

Abstract

This review summarizes clinical experience with infectious disease vaccines and data from animal tumor models that support a paradigm shift for cancer vaccines from therapeutic to prevention applications.

Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

“…Clinical examination and routine blood checks were performed at every visit (weeks 1,2,4,6,8,10,12,14,18,22,24). Patients were assessed for signs of autoimmune disease by measurement of thyroid hormones and pancreatic enzymes, screening for anti-nuclear antibodies as well as monitoring of rheumatoid factor and complement factors.…”

“…[1][2][3] However, tumor vaccination may be appropriate in a more favourable setting, such as minimal residual disease after surgery or successful systemic therapy. 4 Therefore, clinical development of vaccines remains a potentially useful experimental approach. In clinical trials, the most widely used vaccines were antigenic peptides/proteins plus adjuvant or cellular vaccines, such as antigen-loaded dendritic cells or modified tumor cells.…”

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

“…However, this differential efficacy of the cancer vaccine in prophylaxis and therapy has been proven by several other studies evaluating the feasibility of a cancer vaccine with tolerized tumor antigens. [42][43][44][45][46] Novakovic et al 44 found that the proportion of protected mice was 75-100% by vaccination of irradiated melanoma tumor cells with CpG ODN in a prophylactic setting whereas the rates of cured mice were only 11.1-21.1% in a therapeutic setting. Garcia-Hernandez Mde et al 45 recently reported that prophylactic vaccination with a prostate antigen, six-transmembrane epithelial antigen of prostate, significantly delayed tumor growth and improved survival whereas therapeutic vaccination induced a modest delay in the growth of established prostate tumors.…”

CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

“…22 We chose a prophylactic tumor vaccination model since therapeutic vaccination has been largely disappointing during the past decades, whereas vaccines able to induce protective immunity in the situation of minimal residual disease are possibly more appropriate for clinical application. 23 In this study, we asked (1) whether the adjuvant activity of CCL19 can also be observed after intradermal gene gun delivery of DNA, (2) which application route (intramuscular or intradermal) should be preferred for the further preclinical development of a Her2/neu-CCL19 DNA vaccine and (3) which role can be attributed to B cells (which may also express CCR7) in our system.…”