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

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) x 10(10) anti-CD3-activated cells were administered in conjunction with IL-2 in six patients.

Results: Anti-CD3-activated VPLN cells secreted IFN-gamma 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.