CD40-Activated B Cell Cancer Vaccine Improves Second Clinical Remission and Survival in Privately Owned Dogs with Non-Hodgkin's Lymphoma

Abstract

Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendritic cell (DC) vaccine achieving regulatory approval for clinical use last year. Manufacturing remains arduous, especially for DC vaccines, and the prospect of using cell-based immunotherapy in the adjuvant setting or in combination with chemotherapy remains largely untested. Here, we used a comparative oncology approach to test the safety and potential efficacy of tumor RNA-loaded, CD40-activated B cells in privately owned dogs presenting with non-Hodgkin's lymphoma (NHL), a clinical scenario that represents not only a major problem in veterinary medicine but also a bona fide spontaneous animal model for the human condition. When administered to NHL dogs in remission after induction chemotherapy, CD40-B cells electroporated ex vivo with autologous tumor RNA safely stimulated immunity in vivo. Although chemotherapy plus CD40-B vaccination did not improve time-to-progression or lymphoma-specific survival compared to dogs treated with chemotherapy alone, vaccination potentiated the effects of salvage therapy and improved the rate of durable second remissions as well as subsequent lymphoma-specific survival following salvage therapy. Several of these relapsed dogs are now long-term survivors and free of disease for more than a year. Overall, these clinical and immunological results suggest that cell-based CD40 cancer vaccination is safe and synergizes with chemotherapy to improve clinical outcome in canine NHL. More broadly, our findings underscore the unique value of clinical investigations in tumor-bearing companion animals.

Randomized, Placebo-Controlled, Double-Blinded Chemoimmunotherapy Clinical Trial in a Pet Dog Model of Diffuse Large B-cell Lymphoma

“…Therapeutic cancer vaccines target TAAs to induce an active immune response, and 4 earlyphase clinical trials in dogs with B-cell lymphoma have provided a strong rationale for this approach (17)(18)(19)(20). Nevertheless, immunotherapeutic strategies have to face an important obstacle: the ability of tumor cells to evade the immune attack (23).…”

“…Nineteen dogs in complete remission (CR) after induction dose-intense chemotherapy were eligible to be vaccinated. Time to progression (TTP) and lymphoma-specific survival (LSS) were not significantly different between vaccinated and nonvaccinated dogs; however, vaccination potentiated the effects of rescue therapy and improved the rate of durable second remissions and LSS, following salvage therapy (20).…”

“…20). Nineteen dogs in complete remission (CR) after induction dose-intense chemotherapy were eligible to be vaccinated.…”

The properties of human CD40-activated B cells as antigen-presenting cells are not affected by PGE2

“…CD40-activated B cells are currently being studied as an alternative type of APC for cellular vaccines (23)(24)(25)(26). Most importantly, they can be easily expanded ex vivo from peripheral blood of cancer patients (27).…”

<b>Expressão da indoleamina-2,3-dioxigenase em células cancerígenas de pacientes com câncer de mama</b>

“…O epitélio através do sistema lóbulo-alveolar é composto por duas populações celulares, as células mioepiteliais basais e luminais, as quais estão justapostas em uma membrana epitelial contínua. (SORENMO et al, 2011).…”