RADIOIMMUNOTHERAPY OF SOLID CANCERS - A REVIEW

Depending on radionuclide characteristics, radioimmunotherapy (RIT) re lies on radioactivity to destroy cells distant from immunotargeted cel ls. Therefore, even heterogeneous tumors (for antigen recognition) can be treated, because not all cells have to be targeted. Substantial co mplete response rates have been reported in patients with non-Hodgkin' s lymphoma. Much more modest results have been reported for patients w ith bulky solid tumors, e.g. adenocarcinomas. The radiation doses deli vered by targeting antibodies are generally too low to achieve major t herapeutic responses. Dose escalation is limited by myelotoxicity, and higher doses need to be delivered to neoplasms less radiosensitive th an lymphomas. Various trials for both systemic and regional RIT have b een reported on. Intraperitoneal administration has been applied for c olorectal and ovarian carcinomas. Our own results indicate that, e.g., intraperitoneal pseudomyxoma can be treated with RIT. Myelotoxicity c an be reduced by anti-antibody-enhancement, 2- and 3-step strategies, bispecific monoclonal antibodies (MAbs), and extracorporeal immunoadso rption. The radionuclide has to be selected properly for each purpose; it can be a beta-emitter, e.g. I-131, Y-90, Re-188, Re-186, Lu-177 or Sm-153, an alpha-emitter At-211 or Bi-212 or an Auger-emitter, e.g. I -125, I-123. One major problem with RIT, besides slow penetration rate into tumor tissue and low tumor-to-normal tissue ratio, is the HAMA r esponse, which can be partly avoided by the use of humanized MAbs and immunosuppression. However, RIT will be, because of all the recent dev elopments, an important form of cancer management.