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Successful Combination Immunotherapy for the Generation In Vivo of Antitumor Activity With Anti-CD3, Interleukin 2, and Tumor Necrosis Factor

Stephen C. Yang, MD; Kim D. Fry; Elizabeth A. Grimm, PhD; Jack A. Roth, MD

Arch Surg. 1990;125(2):220-225.

Abstract
• The purpose of this study was to generate lymphokine-activated killer cells via alternative pathways using combinations of biologic agents. Immunotherapy with the mouse anti-CD3 analogue combined with low-dose interleukin 2 (IL-2) and tumor necrosis factor (TNF-) was tested for in vivo antitumor efficacy against established pulmonary metastases from a variety of mouse tumor-cell lines. Administration of a single dose of anti-CD3 followed by low-dose IL-2 and TNF- potentiated reduction of metastases compared with higher doses of IL-2 alone or IL-2 plus TNF-. Treatment with anti-CD3 plus IL-2 plus TNF- significantly prolonged survival and resulted in 60% of the mice achieving long-term survival compared with no survival using single agents or other combinations. The lymphokine-activated killer and natural killer activities of mouse splenocytes increased following treatment with anti-CD3 plus IL-2 plus TNF-. These results indicate that the sequential use of anti-CD3, IL-2, and TNF- for the induction and maintenance of lymphokine-activated killer activity potentiates antitumor activity and provides novel strategies for combination immunotherapy.

(Arch Surg. 1990;125:220-225)

Author Affiliations
From the Departments of Thoracic Surgery (Drs Yang and Roth and Ms Fry) and Tumor Biology (Drs Grimm and Roth) and the Division of General Surgery (Dr Grimm), The University of Texas M. D. Anderson Cancer Center, Houston; and the Department of General Surgery, The University of Texas Health Science Center at Houston (Dr Yang).

Footnotes
Accepted for publication October 25, 1989.

Read before the annual meeting of the Society of Surgical Oncology, San Francisco, Calif, May 23, 1989.

Reprint requests to the Department of Thoracic Surgery, Box 109, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030 (Dr Yang).

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