Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non–Small-Cell Lung Cancer

Abstract

Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination.

Lung cancer patients’ CD4+ T cells are activated in vitro by MHC II cell-based vaccines despite the presence of myeloid-derived suppressor cells

“…This approach will only be effective if different lung tumor cells share common antigens. Our findings that T cells primed with an MHC II bronchioloalveolar adenocarcinoma vaccine cross-react with a large cell lung carcinoma, combined with the findings of Raez et al using allogeneic CD80 vaccines [31,32] support this assumption.…”

“…However, this treatment may not be practical for large numbers of patients because it requires the transduction of individual patients' tumor cells [26]. More promising is a vaccine generated by transfecting allogeneic NSCLC cells with the costimulatory molecule CD80 [30,31]. Nineteen patients with advanced disease were treated with this vaccine.…”

Allogeneic tumor cell vaccines

“…58 The ability of this allogeneic vaccine to stimulate a tumor specific CD8 + T-cell response and increase patient survival in patients with advanced disease bodes well for cancer immunotherapies. 55,58 Recently, results from a novel immunotherapeutic approach for the treatment of NSCLC indicate that allogeneic tumor cell lines secreting HSPgp96-Ig show that peptides from allogeneic tumor cells delivered to patients' immune system via gp96 can induce an immune response. 59 While no objective tumor response was observed in clinical trials, stabilization of tumor growth and increased release of IFN-γ by CD8 + T Cells warrant further exploration of similar approaches.…”

“…Recent developments including the identification of lung cancer TAAs ( Table 2), immunosuppressive factors, and the establishment of multiple tumor cell lines have contributed to the growing number of available reagents. 55 The immunotherapeutic Belagenpumatucel-L (Lucanix)…”

“…Patients were vaccinated with an irradiated whole cell allogeneic vaccine (cell line AD100) transfected to express the costimulatory molecule B7-1 along with either HLA-A1 or HLA-A2. 55 The costimulatory molecule B7-1 was administered to boost the expansion of tumor specific immune responses that may help overcome the immunosuppressive environment present in NLSC. The patients were administered a vaccine depending on their HLA type; A1 patients received the A1 vaccine for direct antigen presentation, and non-A1 and non-A2 patients, received an unmatched vaccine (A1) for indirect antigen presentation.…”