Autologous tumor cells/bacillus Calmette-Guérin/formalin-based novel breast cancer vaccine induces an immune antitumor response

Abstract

Autologous cancer cell vaccines represent a multivalent patient-specific treatment. Studies have demonstrated that these immunotherapies should be combined with immunomodulators to improve results. We tested in breast cancer the antitumor effects of a 200 µg autologous tumor cells homogenate combined with 0.0625 mg of bacillus Calmette-Guérin (BCG), and 0.02% formalin. We used a 4T1 murine model of BALB/c receiving four weekly injections of either this vaccine or control treatments. The control treatments were either Phosphate Buffer Saline, BCG treated with formalin, or the tumor cells homogenate plus BCG alone. We found that mice treated with the vaccine had the lowest tumor growth rate and mitosis percentage. The vaccinated group also showed a marked increase in infiltration of antitumor cells (natural killer, CD8+ T and CD4+ Th1 cells), as well as a decrease of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Additionally, we also observed a possible activation of the immune memory response as indicated by plasma cell tumor infiltration. Our results demonstrate that our proposed breast cancer vaccine induces a potent antitumor effect in 4T1 tumor-bearing mice. Its effectiveness, low cost and simple preparation method, makes it a promising treatment candidate for personalized breast cancer immunotherapy.

Evaluation of a ConvitVax/anti-PD-1 combined immunotherapy for breast cancer treatment

“…To date, no immunotherapeutic approach has been found truly effective for breast cancer. Based on the proved success of checkpoint inhibitors, the previously demonstrated antitumor effects of ConvitVax [11] and the potential benefits of using combined therapies [2, 3, 27], we evaluated the effectiveness and possible mechanism of a combined therapy with our vaccine and anti-PD-1.…”

“…However, at the moment of evaluation, the size of the tumor had not yet been significantly reduced. On the other hand, this result could be associated with the high mitotic index, low CD8 + T cells percentage and possible presence of Tregs observed in G4, which positions this combination in disadvantage when compared to the stronger immune response observed in G2 [11].…”

“…The little efficacy of anti-PD-1 monotherapy observed in patients with metastatic breast cancer is partly due to the low number of tumor-infiltrating lymphocytes in most breast cancers [8]. Recently, we showed the effectiveness and ability to induce a significant antitumor cell infiltration by a polyvalent vaccine composed of autologous tumor cells, bacillus Calmette-Guérin (BCG) and formalin in a breast cancer murine model, henceforth referred to as “ConvitVax” [11]. Pre-clinical and clinical studies combining tumor vaccines with checkpoint inhibitors have shown a significant enhancement of the vaccine’s induced immune response and antitumor effects [12–14].…”

Current Approaches in Development of Immunotherapeutic Vaccines for Breast Cancer

“…The vaccine formulation resulted in a lower tumor growth rate and boosted immune cell activation in the mouse model. Promising results in the term of a decrease in the infiltration of suppressor cells and improved immune memory have been observed [27].…”

The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients

“…However, depending on the cancer type, tumor-specific antigens may have a low level of immunogenicity, or the tumor may have a low percentage of unique mutated proteins [11]. Bacterial products can be used to increase the level of immunogenicity to tumor antigens, for example, immune stimulants such as Bacillus Calmette-Guerin (BCG) have been used with irradiated autologous tumor cells in bladder cancer and other tumor types [12,13].…”