ROLE OF NATURAL CYCTOTOXIC CELLS IN LYMPHOMAS

Project Details

Description

Transplantable reticulum cell sarcomas (RCS) of SJL/J mice exhibit several
unique interactions with the host immune system that illustrate important
concepts regarding host-tumor cell interactions. By virtue of their
surface I-As determinants, RCS tumor cells stimulate proliferation of
syngeneic Ly-1+2-T cells and activate NK cells, as a result of which a
variety of lymphokines are also produced, including IL-2, and IFN-gamma.
I-As-specific monoclonal antibodies (McAb) inhibit these in vitro host
responses. Growth of RCS tumor cells in vivo appears dependent on the
host's immune system to generate these responses, since tumor cells do not
grow progressively in immunocompromised SJL recipients or in SJL F1 hybrids
which, because of Ir-genetic restrictions, cannot respond to RCS cells.
Since many of these hypotheses have been formulated on the basis of in
vitro correlates, it is necessary to demonstrate that such interactions
also occur in vivo. The proposed investigation will address this question
in two ways. First, experiments will be performed to define the repertoire
of RCS-reactive cells, using contemporary lymphocyte cloning methodology.
Cloned cell lines with defined functional attributes and/or their soluble
products will be assessed in immunocompromised SJL mice for the capacity to
reconstitute the microenvironment necessary for optimal tumor growth. SJL
"beige" mice will also be used in this study to determine whether the
selective pressure of an NK-deficient environment will influence the
growth, maturation/differentiation and functional characteristics of
primary RCS and transplantable RCS lines. As a secondary aspect of this
investigation, McAb will be produced against cloned RCS-reactive cells.
These McAb will be tested for therapeutic efficacy in inhibiting tumor
growth in vivo by regulating the lymphocyte populations that are necessary
to support the growth of RCS cells. Immunotherapy with I-As-reactive McAb
will also be used to regulate the growth of these I-A+ lymphoma cells.
Once the efficacy of immunotherapy with these McAb has been demonstrated
against the transplantable RCS cell lines, immune intervention in aging SJL
mice will be performed in order to arrest the development of primary RCS
tumors, which occur with high frequency (greater than 90%) in this strain.
Since the RCS tumors of SJL mice have properties in common with some human
B cell malignancies, the proposed investigation will yield a clearer
understanding of host-tumor cell interactions in man and may define new
approaches for the diagnosis and treatment of cancer patients.
StatusFinished
Effective start/end date1/1/906/30/91

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute

ASJC

  • Oncology
  • Cancer Research

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