Prostate cancer vaccines: the long road to clinical application

Abstract

Cancer vaccines as a modality of immune-based cancer treatment offer the promise of a non-toxic and efficacious therapeutic alternative for patients. Emerging data suggest that response to vaccination largely depends on the magnitude of the type I immune response generated, epitope spreading and immunogenic modulation of the tumor. Moreover, accumulating evidence suggests that cancer vaccines will likely induce better results in patients with low tumor burden and less aggressive disease. To induce long-lasting clinical responses, vaccines will need to be combined with immunoregulatory agents to overcome tumor-related immune suppression. Immunotherapy, as a treatment modality for prostate cancer, has received significant attention in the past few years. The most intriguing characteristics that make prostate cancer a preferred target for immune-based treatments are (1) its relative indolence which allows sufficient time for the immune system to develop meaningful antitumor responses; (2) prostate tumor-associated antigens are mainly tissue-lineage antigens, and thus, antitumor responses will preferentially target prostate cancer cells. But, also in the event of eradication of normal prostate epithelium as a result of immune attack, this will have no clinical consequences because the prostate gland is not a vital organ; (3) the use of prostate-specific antigen for early detection of recurrent disease allows for the initiation of vaccine immunotherapy while tumor burden is still minimal. Finally, for improving clinical outcome further to increasing vaccine potency, it is imperative to recognize prognostic and predictive biomarkers of clinical benefit that may guide to select the therapeutic strategies for patients most likely to gain benefit.

Prostate cancer with different ERG status may show different FOXP3-positive cell numbers

“…It is thus of primary importance to recognize additional prognostic parameters, which could potentially be helpful in adjusting appropriate therapy. In this context, the immunological response seems to be worth investigating, and it has already been proposed to use tumor vaccines in prostate cancer [15]. Proper understanding of immunological processes is crucial, as many components of the tumor microenvironment, including macrophages, different classes of lymphocytes, NK cells, plasma cells, neutrophils, eosinophils and mast cells, participate in the immune response [16,17,18,19].…”

A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit

“…The same also applies for preexisting increased IFN-γ immunity along with low TGF-β levels in HLA-A*24 and/or HLA-DRB1*11 carriers, whose combination could be considered as prognostic biomarker for increased OS. Our data are also suggestive for a predictive role of both HLA alleles as well as of IFN-γ and TGF-β for immunological responses to vaccination and clinical outcome [38].…”

Personalized cancer vaccines: Targeting the cancer mutanome

“…In particular, the combination of checkpoint inhibition and personalized vaccine therapy may enhance the immune system’s ability to eliminate tumors by promoting responses to both dominant and subdominant antigens. In addition, it is possible that vaccination to neoantigens will trigger epitope spreading, as has been observed with vaccines to tumor-associated antigens [34, 35]. Of note, whereas the total number of nonsynonymous identified in individual tumors can be as high as several thousand, the final number of validated neoantigens is often much lower, and none may be present in some tumors, as was found for the TRAMP-C1 prostate tumor [33].…”