Adoptive immunotherapy of cancer with polyclonal, 108-fold hyperexpanded, CD4+ and CD8+ T cells

摘要: T cell-mediated cancer immunotherapy is dose dependent and optimally requires participation of antigen-specific CD4+ CD8+ cells. Here, we isolated tumor-sensitized cells activated them in vitro using conditions that led to greater than 108-fold numerical hyperexpansion either the or subset while retaining their capacity for vivo therapeutic efficacy. Murine tumor-draining lymph node (TDLN) were segregated purify CD62Llow subset, thereof. Cells then propagated through multiple cycles anti-CD3 activation with IL-2 + IL-7 IL-23 subset. A broad repertoire TCR Vβ families was maintained throughout hyperexpansion, which similar starting population. Adoptive transfer hyper-expanded eliminated established pulmonary metastases, an immunologically specific fashion without requirement adjunct IL-2. Hyper-expanded cured tumors intracranial subcutaneous sites not susceptible alone. Because accessibility antigen presentation within metastases varies according anatomic site, maintenance a both effector will augment overall systemic efficacy adoptive immunotherapy.