Immunologic Response Elicited in Breast Cancer Patients Receiving a NeuGcGM3-based Vaccine as Adjuvant Therapy

Abstract

This study aimed to investigate the immunogenicity of a cancer vaccine consisting of the NeuGcGM3 ganglioside combined with the outer membrane protein complex of Neisseria meningitides to form very small size particles. The vaccine is administered together with Montanide ISA51, as adjuvant treatment for breast cancer patients. After surgical resection and standard first-line chemo/radiotherapy, breast cancer patients in stage II-III were enrolled in a phase III clinical trial and allocated into 2 strata, according to the number of positive lymph nodes [stratum I (0-3); stratum II (≥4)]. Subsequently, patients were randomly assigned to receive the vaccine or placebo. The treatment consisted of 5 vaccine doses (200 μg) every 2 weeks and thereafter monthly reimmunizations to complete 15 doses. The vaccine was well-tolerated and high titers of immunoglobulin M and immunoglobulin G anti-NeuGcGM3 antibodies were similarly detected in each stratum. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 tumor cell line, and these functional capacities were significantly associated with a better clinical outcome in patients of stratum II. Besides, postimmune sera had the capacity to revert in vitro the immunosuppression induced by NeuGcGM3, as measured by the prevention of CD4 downmodulation on human T lymphocytes. Vaccination had no impact on the frequency of regulatory T cells or circulating NK cells. This study demonstrated, for the first time, the immunogenicity of the NeuGcGM3/VSSP/Montanide ISA 51 vaccine in the adjuvant setting and describes the functionality of induced anti-NeuGcGM3 antibodies as potential surrogate biomarkers of clinical benefit.

Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives

“…Seventeen of them randomly received the vaccine, while the other 5 received the placebo. The treatment was safe and high levels of anti-NeuGc-GM3 antibodies were detected, which was associated with a better clinical outcome [181].…”

Bacteria and Bacterial Components as Natural Bio-Nanocarriers for Drug and Gene Delivery Systems in Cancer Therapy

“…These bacterial polymers hold immense potential in enhancing controlled drug release and osmotic efficacy within the realm of nanomedicine [44]. Bacterial outer membrane proteins derived from Klebsiella pneumonia and Neisseria meningitides have been proven effective as immune adjuvants to activate the immune system for cancer therapy in clinical trials [94,95].…”

Gangliosides generalities and role in cancer therapies

“…For this reason, different strategies are needed to be used in immunotherapies. Examples of those are the use of monoclonal antibodies, adjuvants and/or liposomes 11,13,16,28 .…”

“…Since there was a significant increase in the concentration of anti-NeuGcGM3 IgM and IgG after immunization in both groups of patients (stage I and II). In addition, the majority of patients' hyperimmune sera, not only they could recognize the tumor cells that expressed the NeuGcGM3 ganglioside, but they also had cytotoxic activity on these cells (they killed the cells) 13 .…”

“…In general, gangliosides have been used in immunotherapy as the principal component in different vaccines, whose objective is to increase the immune response of patients towards specific gangliosides that are overexpressed in the membranes of cancer cells [10][11][12] . Some of these studies have shown good results [11][12][13][14][15] . In consequence, we consider them as promising proposals in cancer treatment.…”