Year: 1995
Type: article
Abstract: Immunotherapy with cytokines or cytokine-activated effector cells is a promising therapeutic approach, which has not been extensively evaluated in patients with head and neck cancer (HNC). Preclinical data obtained with human effector cells, both MHCrestricted cytolytic T lymphocytes (CTL) and MHC-nonrestricted natural killer (NK) cells, indicate that it is feasible to generate such cytokine-activated effector cells in patients with advanced HNC. Technology for separation of human effector cells and their culture on a therapeutic scale is available. Purified subsets of lymphocytes derived from autologous peripheral blood, lymph node lymphocytes or tumor-infiltrating cells can be consistently prepared by immunoselection in patients with HNC, evaluated for antitumor efficacy in vitro, using 51Cr-release assays, monolayer cultures or tumor spheroids and used for adoptive transfers. Locoregional transfer of such immune cells plus cytokine (s) can effectively inhibit growth of squamous cell carcinoma of the head and neck (SCCHN) xenografts established in nude mice. Human IL2-activated NK cells (A-NK) have been shown to preferentially enter SCCHN spheroids and kill or inhibit growth of tumor cells in spheroids or in SCCHN xenografts established in nude mice. A-NK cells can be armed in vitro with chimeric monoclonal antibodies selectively reactive with squamous epithelia (e. g., cMAbs E48 or U36) to optimize their targeting to the tumor. In vivo arming with these cMAbs is likely to increase anti-SCCHN responses. Supernatants of A-NK cells cultured in the presence of IL2 have been shown to arrest SCCHN cells in the G0/G1 phase of the cell cycle and to inhibit growth of SCCHN xenografts in nude mice. Efforts to transduce A-NK cells with cytokine genes are in progress. An urgent need exists in head and neck oncology for effective adjuvant therapy, and immunotherapy with immune effector cells should be considered as a feasible therapeutic modality in the adjuvant setting in HNC.
DOI: 10.2468/jbes.46.71
Author: Theresa L. Whiteside
Institution: University of Pittsburgh
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2000271711