B-Cell Epitope Peptide Cancer Vaccines: A New Paradigm for Combination Immunotherapies with Novel Checkpoint Peptide Vaccine

Abstract

In light of the numerous US FDA-approved humanized monoclonal antibodies (mAbs) for cancer immunotherapy, it is surprising that the advancement of B-cell epitope vaccines designed to elicit a natural humoral polyclonal antibody response has not gained traction in the immune-oncology landscape. Passive immunotherapy with humanized mAbs (Trastuzumab [Herceptin®]; Pertuzumab [Perjeta®]) has provided clinical benefit to breast cancer patients, albeit with significant shortcomings including toxicity problems and resistance, high costs, sophisticated therapeutic regimen and long half-life. The role of B-cell humoral immunity in cancer is under appreciated and underdeveloped. We have advanced the idea of active immunotherapy with chimeric B-cell epitope peptides incorporating a ‘promiscuous’ T-cell epitope that elicits a polyclonal antibody response, which provides safe, cost–effective therapeutic advantage over mAbs. We have created a portfolio of validated B-cell peptide epitopes against multiple receptor tyrosine kinases (HER-1, HER-3, IGF-1R and VEGF). We have successfully translated two HER-2 combination B-cell peptide vaccines in Phase I and II clinical trials. We have recently developed an effective novel programmed cell death-1 vaccine. In this article, I will review our approaches and strategies that focus on B-cell epitope cancer vaccines.

Clinical and Immunologic Responses to a B-Cell Epitope Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer—Results from Phase Ib Trial IMU.ACS.001

“…As described for trastuzumab, selective pressure on HER2 might also be exerted by vaccine-induced HER2specific Abs, giving HER2-negative cancer cell clones a survival advantage which eventually leads to tumor progression (45). This indicates that efforts to overcome treatment limitations due to loss of HER2-expression may have to extend to immunizations with cancer vaccines (46), possibly in the form of combining the IMU-131 vaccine with check point inhibitors as we recently demonstrated in a pre-clinical setting (17).…”

Vaccination against Her-2/neu, with focus on peptide-based vaccines

“…This allows MCH class IImediated activation of multiple T helper cells, leading to increased production of also tumor peptide-specific Ab production by B cells. 84 A vaccine, B-Vaxx, consisting of a mixture of the two chimeric constructs in combination with a potent adjuvant nor-muramyl dipeptide (n-MDP) and emulsified in Montanide ISA 720, was formulated. 84 In a recent study, the use of a liposomal system for the delivery of B-cell peptide of Her-2/neu was also investigated.…”

“…84 A vaccine, B-Vaxx, consisting of a mixture of the two chimeric constructs in combination with a potent adjuvant nor-muramyl dipeptide (n-MDP) and emulsified in Montanide ISA 720, was formulated. 84 In a recent study, the use of a liposomal system for the delivery of B-cell peptide of Her-2/neu was also investigated. 85 The liposomal system was composed of a spatially separated B-cell epitope of the Her-2/neu ECD targeted by pertuzumab, and ovalbumin peptide OVA (amino acids 323-339), to provide non-cognate T-cell support.…”

Extracellular Vesicles and Their Current Role in Cancer Immunotherapy

“…It is also important to mention another peptide-based vaccine, HerVaxx. It consists of three peptides isolated from HER2 extracellular domain and linked to another carrier protein that is diphtheria toxin [ 82 ]. In the last few months a Phase 2 HerVaxx study was updated to evaluate the overall survival and the progression-free survival and to measure the efficacy, safety and immune response in 68 patients with metastatic gastric cancer overexpressing the HER-2 protein (NCT02795988).…”