Genetically engineered antibodies for direct antineoplastic treatment and systematic delivery of various therapeutic agents to cancer cells

Classical antineoplastic therapeutic modalities such as surgery; radiation, and chemotherapy not only fail to cure the great majority of neoplasms, bu t their employment often leads to severe and debilitating side effects asso ciated with severe neoplasm-related morbidity. Immunotherapy as a fourth mo dality of anti-cancer therapy has already been proven to be quite effective . The astonishing immunophenotypic (IP) heterogeneity of neoplastic cells, the different cytotoxic activity associated with the moiety linked to given monoclonal antibodies (mAb), and mostly the impressive genetic modulation capabilities of cancer cells still remain as yet unsolved difficulties in t he present immunotherapy of human neoplasms. The advances in mAb production have revitalised the initial concept of use of cancer cell specific "magic bullets.' Antibodies represent new approaches to anti-cancer therapy: they are neoplastic cell-specific and lethal to neoplastically transformed cell s via immune effector mechanisms with no toxicity to normal tissues. They a re being observed and developed, adhering to the old prayer: "Destroy the d iseased tissues, preserve the normal." Strategies for the employment of ant ibodies include: 1) immune reaction directed destruction of neoplastic cell s; 2) interference with the growth and differentiation of malignant cells; 3) antigen epitope directed transport of anti-cancer agents to neoplastic c ells; 4) anti-idiotype tumour vaccines; and 5) development of engineered (h umanized) mouse mAbs for anticancer therapy. In addition, a variety of agen ts (e.g. toxins, radionuclides, chemotherapeutic drugs) have been conjugate d to mouse and human mAbs for selective delivery to neoplastic cells.