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In Vitro and in Vivo Effects of a Monoclonal Antibody-Toxin Conjugate for Use in Autologous Bone Marrow Transplantation for Patients with Breast Cancer

Ludwig Institute for Cancer Research (London Branch), at St. George's Hospital Medical School, London SW17 ORE [R. C. C.] and at Royal Marsden Hospital, Sutton, Surrey SM2 5PX [R. B., M. J. O., A. M. N.]; The Royal Marsden Hospital, Sutton, Surrey SM2 5PX [R. C. C., V. S., M. V., T. J. P.]; and The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB [J. A. F.], United Kingdom

We have devised a method utilizing a monoclonal antibody-toxin conjugate (LICR-LON-Fib75/abrin A-chain) for ridding bone marrow of infiltrating breast cancer cells to rescue patients with autologous bone marrow following high dose therapy.

Initially we examined the activity of this conjugate in vitro. Five of seven human breast cancer cell lines were killed following exposure at 10^-8 M for 2 h; this concentration only reduced bone marrow colony formation to 83% (range, 50–100%) of control bone marrow.

We then examined the pattern of bone marrow recovery after high dose melphalan (200 mg/m²) in patients with advanced breast cancer who were in remission following combination chemotherapy. To do this we compared the time of recovery of the blood count in three patients who received treated marrow and seven who received untreated marrow. Mean time to recovery of the peripheral white count (>1.5 x 10⁹/liter) was 16.7 days (treated) and 18.3 days (untreated), respectively. Mean time to recovery of peripheral platelet count (>50 x 10⁹/liter) was 23.7 days (treated) and 18.9 days (untreated), respectively.

Patients continued in remission for 1->14 mo after high dose melphalan, and remission duration was similar in patients who received treated (6.2 mo) and untreated (7.3 mo) bone marrow.

These findings indicate that treatment of bone marrow with LICR-LON-Fib75/abrin A-chain conjugate does not significantly impair bone marrow recovery, and it is, therefore, possible to rescue breast cancer patients with bone marrow that has been cleansed of infiltrating cancer cells. This may have an application in patients with poor-risk primary breast cancer who have micrometastases and who may benefit from intensive therapy, but it has minimal application in patients with more advanced disease.

¹ To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research (London Branch), St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom.

Received 8/28/85. Revised 4/ 8/86. Accepted 4/25/86.

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