Antigen‐specific immunotherapy of cervical and ovarian cancer

Abstract

We contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types causes cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T-cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast, little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA, because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface, and potentially contributes to ovarian cancer biology.

Tumour-associated antigens: considerations for their use in tumour immunotherapy

“…The E6 and E7 proteins produced by human papilloma virus (HPV), the LMP and EBNA proteins of Epstein-Bar virus (EBV), Tax protein from human T lymphotrophic virus-1 (HTLV-1) and HCVcore protein of hepatitis C virus (HCV), amongst many others, are all major contributors to the malignant phenotype [36][37][38][39][40][41][42][43]. Such antigens are necessary for maintaining the malignant behaviour of cells and therefore serve as relevant targets for immunotherapy [44][45][46][47]. For example, LMP and EBNA of EBV are thought to be involved in immortalisation and interaction with c-myc to affect signalling pathways leading to formation of lymphomas such as Burkitt's lymphoma [38,39].…”

Papillomavirus Prophylactic Vaccines: Established Successes, New Approaches

“…Treatments of warts in patients often employ destruction of local tissue, like cryotherapy, or nonspecific immunostimulatory agents, including a Toll-like receptor (TLR) agonist delivered topically. Furthermore, warts are typically recalcitrant in HIV-positive or organ transplant patients, further suggesting the importance of cellular immune responses in clearing HPV infections and the potential of therapeutic HPV vaccination (45). Despite poor recognition of the viral proteins by the host immune cells, the viral proteins are immunogenic, especially the late ones, as shown by their experimental inoculation in cattle and rabbits (16,48,59).…”

Human Papillomavirus Immunogen That Provides Protective Tumor Immunity and Induces Tumor Regression

“…Included in these trials, there have been peptide-based HPV vaccines consisting of overlapping peptides covering the E6/E7 antigens, and presenting enough epitopes to partially overcome MHC restriction (13,16). Such peptide vaccines have been well tolerated in preclinical and clinical trials, and have proven capable of generating antigen-specific T-cell responses to a broad spectrum of E6/E7 epitopes in some patients with premalignant lesions associated with HPV (20,23,40). However, the clinical efficacy of such peptide vaccines as therapeutic modalities remains to be determined in patients with carcinoma in situ, and ideally these therapeutic vaccines could target both premalignant lesions and cervical carcinoma (24,28,33,35).…”