Document 0778
 DOCN  M94B0778
 TI    Bispecific antibodies recruiting cellular effectors (Meeting abstract).
 DT    9412
 AU    Thielemans K; Lab. of Physiology-Immunology, Vrije Universiteit Brussel,
       B-1090; Brussels, Belgium
 SO    EACR-12: 12th Biennial Meeting of the European Association for Cancer
       Research. April 4-7, 1993, Brussels, Belgium, 1993.. Unique Identifier :
       AIDSLINE ICDB/94697527
 AB    The idea to target T lymphocytes toward tumor cells has been tested
       extensively and successfully by many laboratories. Our laboratory has
       evaluated this attractive approach in vivo. We have developed bispecific
       antibodies by hybrid-hybridoma technique, with dual specificity: the
       murine CD3 complex and the idiotype (tumor specific antigen) of the
       surface expressed IgM on two murine B-cell lymphomas. Since the primary
       goal of our experiments was to evaluate the therapeutic potential of
       this approach in vivo, we have invested great efforts in the generation
       of proper control reagents. Using the aggressive 38C13 lymphoma of C3H
       origin, we showed that bispecific antibodies could cure a significant
       number of tumor-bearing animals. Animals with even a lower tumor burden
       were not protected with any of the control antibodies (bi- or univalent
       class-matched anti-idiotype mAb, bi- or univalent anti-CD3 mAb).
       Tumor-bearing C3H/HeJ mice (not able to perform FcR-dependent ADCC)
       could also be successfully treated. Animals in which we had induced
       allo-sensitized effector T cells showed a much higher cure rate in
       comparison with the experiments in untreated animals. Further evidence
       that the therapeutic effect was T-cell-mediated and dependent on the
       bridge formation between tumor cells and T cells, was obtained by using
       a tumor-antigen negative variant of the 38C13 tumor line and by using a
       mixture of a T-cell binding/nontumor-cell binding antibody plus a
       tumor-cell binding/nonT-cell binding antibody. Similar results were
       obtained with the BCL1 lymphoma model in BALB/c mice. The efficacy of
       the bispecific antibodies was dependent on both tumor load and dose.
       Repeated injections of bispecific antibodies could cure more mice than a
       single injection. Treatment of tumor-bearing mice in which either CD4+,
       CD8+ or both subsets had been depleted, clearly indicated the
       T-cell-mediated effect and the contribution of both subsets to the tumor
       eradicating mechanism. Taken together, our data indicate that it is
       indeed possible to recruit and focus T cells against a given target in
       vivo. Ongoing experiments explore the T-cell-mediated mechanism and the
       potential improvement of our results by combining two bispecific
       antibodies which will activate the T cells at the tumor site via CD3 and
       CD28.
 DE    Animal  Antibodies/*ADMINISTRATION & DOSAGE  CD4-CD8 Ratio
       *Immunotherapy  Lymphoma/IMMUNOLOGY/*THERAPY  Mice  Mice, Inbred BALB C
       Mice, Inbred C3H  T-Lymphocytes/IMMUNOLOGY  MEETING ABSTRACT

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