Immunotherapy at Large: The Road to Personalized Cancer Vaccines

“The field of tumor immunology has been flooded with exciting therapeutic advances on many fronts. Immunotherapies targeting T cell inhibitory molecules have proven highly effective in some cancers, but additional strategies to induce tumor immunity, such as cancer vaccination, could further increase tumor killing. The combination of both will probably be the way forward in future immunotherapy. In ‘Bedside to Bench’, Robert Vonderheide and Katherine Nathanson discuss the potential of cancer genomics to identify specific tumor mutations in patients that may be used as targets in cancer vaccines to overcome problems linked to self-antigen epitopes used nowadays. Despite the existing biological and technical hurdles, a framework to implement personalized cancer vaccines in the clinic may be worth considering. In ‘Bench to Bedside’, Glenn Dranoff peruses the clinical efficacy and detrimental effects of two T cell immune-checkpoint inhibitors, alone and in combination, in patients with melanoma. The studies underscore the need to continue investigating specific tumor events directly involving tumor evasion to develop combinatorial strategies that will reduce drug-related pathology while achieving anti-tumor efficacy.”

Tumor-Specific T-cell Help Is Associated with Improved Survival in Melanoma

“Despite success with immune checkpoint inhibitors, clinical benefit from cancer vaccines remains elusive. Combined targeting of melanoma-specific CD4+ and CD8+ T-lymphocyte epitopes was associated with improved survival compared with targeting either alone, or when a nonspecific helper epitope was used. We discuss the potential role of antigen-specific CD4 help.”

A Randomized Phase II Trial of Multiepitope Vaccination with Melanoma Peptides for Cytotoxic T Cells and Helper T Cells for Patients with Metastatic Melanoma (E1602)

“Purpose: This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine and improve clinical outcome in patients with advanced melanoma. Experimental Design: One hundred seventy-five patients with measurable stage IV melanoma were enrolled into 4 treatment groups, vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CTL (12MP, group A), plus a tetanus peptide (group B), or a mixture of 6 melanoma helper peptides (6MHP, group C) to stimulate helper T lymphocytes (HTL), or with 6 melanoma helper peptide (6MHP) alone (group D), in incomplete Freund’s adjuvant plus granulocyte macrophage colony-stimulating factor. CTL responses were assessed using an in vitro-stimulated IFN-γ ELIspot assay, and HTL responses were assessed using a proliferation assay.”

New Cancer Vaccine Enters Phase IIb Clinical Trial for Patients with CRPC

CureVac, a German biopharmaceutical company, announced the start of a phase IIb clinical trial of its vaccine, CV9104, for castration-resistant prostate cancer (CRPC). The vaccine works by prompting the body’s own immune system to attack prostate cancer cells. The trial will enroll up to 200 patients across eight European countries who have never received chemotherapy for CRPC. For more information on the clinical trial click here.

CureVac Initiates Phase 2b Clinical Trial of its mRNA-Based Cancer Vaccine in Patients with Castration-Resistant Prostate Cancer

CureVac GmbH, a clinical stage biopharmaceutical company that has pioneered the development of a new class of therapies and vaccines based on messenger RNA (mRNA), today announced that it has initiated a double-blind, randomized Phase 2b clinical trial of its RNActive® cancer vaccine, CV9104, for the treatment of patients with castration-resistant prostate cancer.”

Serum Antibodies Can Predict Survival for Patients Treated with the Vaccine PROSTVAC-VF

The pre-vaccination IgM antibodies to anti-BG-Atr were significantly associated with survival in patients with advanced prostate cancer treated with PROSTVAC-VF. This antibody may be a predictive biomarker for response to PROSTVAC-VF if validated.