Introduction to the Tenth Conference on Cancer Therapy with Antibodies and Immunoconjugates

Cancer immunotherapy has come of age. Already seven antibody products have been approved as cancer therapeutics—five as naked monoclonal antibodies (mAb), one as a drug immunoconjugate, and two as radioimmunotherapy agents (1)—and the current buzzword is “targeted therapy.” I like to think that our endeavors with radiolabeled antibodies, represented in the proceedings of these conferences over the past 25 years (2–10), perhaps served as an impetus for the identification and development of various forms and uses of mAbs targeted against cancer antigens and receptors. Indeed, we have transitioned from polyclonal antibodies to murine monoclonal, chimeric, and humanized mAbs, from ¹³¹I to ¹¹¹In, ^99mTc, ⁹⁰Y, ²¹³Bi, to ¹⁷⁷Lu, and from direct antibody radiolabeling to pretargeting methods.

Paradoxically, the success in introducing unconjugated, or naked, mAbs in the treatment of cancer, usually in combination with cytotoxic drugs, has not had a commensurate influence on promoting research on radiolabeled antibodies despite their usually being more potent than naked mAbs, because the labeled mAbs are more complicated to use and require the participation of nuclear physicians or radiation therapists for their dispensing. For example, radiolabeled forms of tositumomab (Bexxar) and ibritumomab (Zevalin) have shown a more significant efficacy in non-Hodgkin's lymphoma patients than their naked anti-CD20 mAb counterparts (11, 12). Hence, cancer radioimmunotherapy is at a crossroads, because the modest (or almost disappointing) adoption of the first two approved radioimmunotherapy agents for non-Hodgkin's lymphoma therapy has discouraged its commercial development and, in turn, academic research. Yet, as shown in the articles in this supplement, new radiolabeled antibody constructs, delivery methods, and tumor targets are being introduced and studied. Investigators are gaining a better understanding of the problems and prospects of incorporating radiolabeled antibodies into combination therapies. Thus, I remain convinced that radioantibodies also will become an option in the armamentarium of solid cancer therapeutics.

This Tenth Conference, which included over 40 presentations, is represented here by 21 articles that span the use of antibodies, drug immunoconjugates, and radioimmunoconjugates of various types for a number of different cancers, both hematologic and solid tumors. I am especially pleased that four articles involving two different approaches of pretargeting are included. Pretargeting is a new method of radioimmunotherapy whereby the tumor-targeting naked mAb is separated from the subsequent delivery of a radioactive effector molecule, and which seems to improve tumor-to-background ratios and the radiation doses delivered to the tumor, as reviewed recently (13–15).

I thank the Program Committee for chairing the various sections of the conference and reviewing the manuscripts. I also thank my co-chairman, Dr. Sally J. DeNardo, for helping in the organization of the conference and her many contributions during the conference and in these proceedings. We were particularly honored in having Phil Gold, M.D., Ph.D., the codiscoverer of carcinoembryonic antigen 40 years ago (16), in attendance and stimulating us with a dinner lecture on his perspectives of the philosophy of science and medical research. I am also grateful to Rosaleen Church for succeeding in collecting the manuscripts and their reviews in time for publishing these proceedings within a year of the conference. Of course, the conference and these proceedings would not be possible without the scientific contributors, the generous support of several companies, and conference grants from the National Cancer Institute and the New Jersey Commission on Cancer Research.