Since antibodies were first described in the late 1800s, scientists have wondered whether these proteins might be manufactured or manipulated to attack cancer cells. However, propagating cells that could churn out a specific antibody remained a stumbling block until 1975, when immunologists Georges J.F. Köhler and César Milstein fused a mouse myeloma cell and a B cell, forming a hybridoma. This cell pumped out antibodies that were identical clones.
But researchers met with little success in using monoclonal antibodies (mAb) to treat human cancer because tumor-specific antigens hadn't been identified in humans. “In the mid-1980s, the field was dead in the water,” recalls Lee M. Nadler, MD, who joined Dana-Farber Cancer Institute (DFCI) in 1977.
Nadler and his team immunized mice with cells from a patient with Burkitt's lymphoma, and in 1979 created a hybridoma that produced a mAb that only reacted with the patient's normal and cancerous B cells. Because it was the first B-cell–specific antigen ever discovered, they named the antigen B1. (Nadler, now senior vice president of Experimental Medicine at DFCI and dean for Clinical and Translational Research at Harvard, renamed it CD20 in 1985.)
In 1979, Nadler also treated a patient with a mAb for the first time in the world.
After the advent of recombinant DNA tools, in 1991 IDEC Pharmaceuticals began to develop a mAb that latched on to the CD20 antigen, which sticks out of the surface of B cells, to treat non-Hodgkin lymphoma. Known as rituximab (Rituxan; Biogen Idec), the mAb drug induced apoptosis, activated complement, and recruited macrophages and other effector cells to slay tumor cells.
In clinical trials conducted at Stanford, M.D. Anderson Cancer Center, and other institutions, more than 40% of patients responded to rituximab alone. When it was combined with a standard chemotherapy, patients lived significantly longer. “It did just what we engineered it to do,” says Antonio Grillo-López, MD, who was chief medical officer at IDEC Pharmaceuticals from 1992 to 2001.
Approved in 1997, rituximab was the first mAb approved to treat cancer. Today, more than a dozen such agents, including the breast cancer drug trastuzumab (Herceptin; Genentech), have been approved.
This article is the fourth in a 5-part series commemorating the passage of the National Cancer Act in 1971.
For more news on cancer research, visit Cancer Discovery online at www.AACR.org/CDnews.