Generation of vaccine-primed lymphocytes for the treatment of head and neck cancer

Background. This study was performed to assess the ability of autologous tumor vaccines to induce T-cell reactivity to squamous cell cancers (SCC). Methods. Irradiated autologous tumor cells admixed with bacillus Calmette-Guérin (BCG) were given intradermally in patients with advanced head and neck cancers. Vaccine-primed lymph node (VPLN) cells were secondarily activated with anti-CD3 mAb and expanded in IL-2 for adoptive immunotherapy. A mean (± SEM) of 2 (±0.6) × 10¹⁰ anti-CD3-activated cells were administered in conjunction with IL-2 in six patients. Results. Anti-CD3-activated VPLN cells secreted IFN-γ and GM-CSF in response to autologous tumor cells but not to allogeneic tumor cells in four of five patients analyzed. Both CD4⁺ and CD8^- tumor reactive cells were present in the VPLN. There were no significant tumor responses after transfer of the anti-CD3-activated VPLN. In separate experiments, costimulation of VPLN cells with anti-CD3 and anti-CD28 mAb resulted in enhanced cytokine secretion to autologous tumor compared with anti-CD3 activation alone. Conclusions. Both CD4⁺ and CD8⁺ responses can be induced to SCC by autologous tumor vaccination. However, additional approaches need to be identified to enhance the therapeutic efficacy of this approach.