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

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Abstract
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. © 2003 Wiley Periodicals, Inc. Head Neck 25: 198–209, 2003