Polymeric conjugates of L-
asparaginase and an excess of homologous
albumin were compared with free L-
asparaginase for antitumor activity using a mouse model 6C3HED
lymphosarcoma and a human pancreatic tumor cell line, PANC-1. The
asparaginase-
albumin polymer is more resistant to proteolytic degradation compared to equivalent amounts of free
enzyme and is more effective as an
antitumor agent in prolonging survival of C3H/HeJ mice receiving 6C3HED
lymphosarcoma. In terms of antitumor activity, the
enzyme is approximately 20 times more effective, compared to free
enzyme, when given in polymeric form with
albumin. Similarly, the polymeric form of L-
asparaginase is more effective in inhibiting cell growth of human pancreatic
tumor cells grown in tissue culture. The increased effectiveness of the polymeric form of L-
asparaginase is probably related to its resistance to biodegradation. The use of cell surface-specific
monoclonal antibodies to target the
polymer to
tumor cells is also demonstrated.