Methods for Optimizing CATS Immunotherapeutics into Humanized Derivatives with Reduced Autoreactivity, Reduced Toxicity and Enhanced Long-Term Efficacy

摘要

The present invention describes unique means for reducing autoreactivity that sensitizes against sustained treatments, and toxicity associated with administration of biologicals, in order to develop safer cancer immunotherapeutics. Short functional sequences are identified in the biologic and matched to their most homologous human counterpart. The human homologs are swapped in to replace their foreign counterparts. Alternatively, variants are selected that have exhibit less toxicity in human or primate experiments from nature, and these sequences are swapped in to replace their counterparts in the biologic. Also, human sequences that mediate the same function as foreign sequences in the biologic, but lack any sequence homology, can be swapped in for their foreign sequence counterparts. These inventions are applied to derivatize the HIV/SIV Tat protein into humanized trimers (CATS) useful for the treatment of cancer.