We present data providing new evidence that poly[N-(2-hydroxypropyl)
methacrylamide] (PHPMA)-bound drugs, unlike free drugs, have both
cytostatic and immunomobilizing activity (CIA). Immediately after injection, due to the high level of the
drug, the main activity of the polymeric conjugate is cytotoxic and
cytostatic. Later on, long-term circulating PHPMA-bound
drug, at concentrations lower than its minimal inhibitory levels, mobilizes the defense mechanisms of the host. Cytotoxic and
cytostatic effects of
drug-PHPMA were repeatedly confirmed. The following data support the concept of the immunomobilizing activity of the
N-(2-hydroxypropyl)methacrylamide (
HPMA) conjugates: (a) pre-treatment with free drugs (
doxorubicin,
cyclosporin A) accelerates the appearance of EL4 mouse
T-cell lymphoma while a similar pre-treatment with
doxorubicin-PHPMA induces limited but definitive mobilization of the host's defense mechanisms; (b) mice cured of EL4 mouse
T-cell lymphoma, BCL1 mouse
B-cell leukemia and 38C13 mouse
B-cell lymphoma by injection of
doxorubicin-PHPMA conjugate targeted with
monoclonal antibodies (anti-Thy 1.2 for EL4, anti-B1 for BCL1 and anti-CD71 for 38C13) and re-transplanted with a lethal dose of the same
cancer cells survive without any treatment considerably longer than control mice; (c) increased NK activity and anti-
cancer antibody was detected only in animals treated with
doxorubicin-PHPMA conjugate; and (d) considerably increased NK and LAK activity was seen in a human patient treated for generalized
breast carcinoma with
doxorubicin-PHPMA-
IgG.