Retroviral Vector Targeting to Melanoma Cells by Single-Chain Antibody Incorporation in Envelope

Two strategies for targeting recombinant retroviruses to melanoma cells were compared. One was to extend the tropism of an ecotropic envelope to human melanoma cells, the other was to enhance the tropism of an amphotropic envelope for melanoma cells. Chimeric retroviral envelopes, incorporating a single-chain antibody (ScFv) directed against high-molecular-weight melanoma-associated antigen (HMWMAA) at the amino terminus are correctly processed and incorporated into virions. ScFv-ecotropic envelope chimeras allow specific, but low-titer, targeting of HMWMAA-positive cells, when co-expressed with ecotropic envelopes. ScFv-amphotropic envelope chimeras bind specifically to HMWMAA-positive cells and allow preferential infection at high titer.

Overview summary

In most current cancer gene therapy, tumor cells are removed by biopsy and genetically modified ex vivo before being returned to the patient. This method is slow and costly and is limited to those patients from which a biopsy can be readily taken. For cancer gene therapy to have widespread clinical application it will be necessary to avoid ex vivo gene transfer. To do this, vectors must be developed that only transduce target tumour cells and not other surrounding cells. In this study our aim was to generate retroviral vectors that specifically infect melanoma cells.