Cancer Immunotherapy - The Endgame Begins

June 18, 2008

Louis M. Weiner, M.D.

In 1987, an editorial accompanying a report on the use of high-dose

interleukin-2 therapy for cancer asked whether the field of immunotherapy was at

" the beginning of the end " or " the end of the beginning. " 1 In retrospect, I

would say it was at the " beginning of the beginning. " Have we made progress

since then? Finn, in her review of tumor immunology in this issue of the Journal

(pages 2704-2715), answers emphatically in the affirmative, and the report by

Hunder et al., also in this issue (pages 2698-2703), underscores the remarkable

potential of the immune system to eradicate cancer, even when the disease is

widespread.

It has long been known that graft-versus-tumor effects underlie the success of

allogeneic bone marrow transplantation for hematologic neoplasms and the

efficacy of donor lymphocyte infusions in chronic myelogenous leukemia. These

new results show that the immune system can eradicate a cancer, just as it can

reject an allogeneic organ unless the recipient receives potent

immunosuppressive agents. However, since the immune system perceives most

cancers as " self, " the allograft-rejection mechanism is not often operative in

patients with cancer.

Nevertheless, the immune system can respond to some types of tumors.

Interactions of developing tumors with the immune system can eliminate cancer

cells that display highly immunogenic tumor antigens, thereby shaping the

tumor's repertoire of cancer antigens and enhancing the ability of the surviving

tumor cells to evade the immune system. It is also possible to activate the

immune system into an antitumor state. About 15% of patients with metastatic

melanoma or renal-cell carcinoma have clinically significant responses to

activation of T cells by high-dose interleukin-2 therapy. Some of these

responses are complete, durable, and apparently curative. Recently, et

al. improved on these results by treating melanoma with lymphocytotoxic

chemotherapy, followed by an infusion of autologous tumor-derived T cells in

conjunction with interleukin-2 to sustain T-cell survival and activation.2

Hence, there is a precedent for the remarkable results of the adoptive cellular

therapy approach described by Hunder et al. These successes indicate that it is

possible to induce a restricted kind of autoimmunity, targeted primarily against

cancer-related antigens, with limited toxic effects on the patient.

if you cannot access this encouraging perspective, let me know. ~ Karl

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