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Blood, Vol. 95 No. 7 (April 1), 2000:
pp. 2426-2433
Immunization of allogeneic bone marrow transplant recipients with
tumor cell vaccines enhances graft-versus-tumor activity without
exacerbating graft-versus-host disease
Larry D. Anderson Jr.,
Cherylyn A. Savary, and
Craig A. Mullen
From the Departments of Experimental Pediatrics, Immunology, and
Surgical Oncology, The University of Texas M.D. Anderson Cancer Center,
Houston, TX.
Allogeneic bone marrow transplantation (BMT) induces 2 closely
associated immune responses: graft-versus-tumor (GVT) activity and graft-versus-host disease (GVHD). We have previously shown that pretransplant immunization of allogeneic BMT donors with a
recipient-derived tumor cell vaccine increases both GVT activity and lethal GVHD because of the priming of donor T cells against putative minor histocompatibility antigens (mHAgs) on the tumor vaccine cells. The work reported here tested the hypothesis that tumor
cell vaccination after BMT would produce an increase in GVT activity
without exacerbating GVHD. C3H.SW donor bone marrow and splenocytes
were transplanted into major histocompatibility complex-matched,
mHAg-mismatched C57BL/6 recipients. One month after BMT, recipients
were immunized against either a C57BL/6 myeloid leukemia (C1498) or
fibrosarcoma (205). Immunized recipients had a significant increase in
survival and protection against tumor growth in both tumor models, and
significant tumor protection was seen even in recipients with
preexisting micrometastatic cancer before immunization. Alloreactivity
appeared to contribute to the in vitro anti-tumor cytolytic activity,
but in vivo immunity was tumor specific, and no exacerbation of GVHD
was observed. Although the immunodominant mHAg B6dom1 was
shown to be expressed by all B6 tumors tested and was largely responsible for the alloreactivity resulting from tumor immunization of
donors, the in vitro alloreactivity of immune recipients was more
restricted and was not mediated by recognition of B6dom1.
In conclusion, post-transplant tumor immunization of allogeneic BMT
recipients against either a leukemia or a solid tumor can increase GVT
activity and survival without exacerbating GVHD.
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