Stable expression of a retrovirally transferred adhesion molecule in a human tumor-specific CTL clone. Perspectives for the ex vivo manipulation of effector cells used in adoptive immunotherapy.

Abstract

The adoptive transfer of in vivo activated effector cells for cancer treatment [1] has one major drawback: in vitro activated lymphocytes display altered features of homing upon retransplantation and frequently are trapped in the spleen and the lung [2]. One possibility to restore natural homing features could be based on the in vitro transfer of appropriate homing molecules. Since cutaneous lymphoma [Wagner S, submitted], locally growing melanoma and skin metastases of malignant melanoma [3] express high levels of a CD44 variant isoform containing exon vlO, we speculate that CD44v10 may be a particular homing receptor allowing lymphocytes to infiltrate epidermal tissue. Based on these considerations we explored the possibility of transfecting a human in vitro generated melanoma-specific CTL clone with this particular CD44 isoform. We explored the feasibility of a stable gene transfer into human CTL. Here we report on a protocol where a human melanoma-specific CTL clone stably expressed a homing receptor after retroviral transfection.