autologous blood and marrow transplantation - Blog Science ...

218 Chapter 5: Myeloma
PBSC transplantation; concomitantly, an ex vivo expansion of their T cells is
undertaken, using CD40-activated "y-irradiated autologous MM cells as
stimulators. Preliminary studies suggest that these T cells can be expanded
effectively to the level of 10 8
—10 9
and safely administered as adoptive
immunotherapy. In vitro studies show their reactivity with autologous MM cells,
but not with autologous B cells, CD40-activated autologous B cells, or allogeneic
MM cells. The clinical utility of this treatment is under active investigation. A
second strategy for enhancing autologous immunity to MM posttransplant involves
vaccines. One example at our institute involves vaccinations with fusions of MM
cells with DCs (MM-DC fusions). We have pioneered vaccinations with MM-DC
fusions or with transduced DCs in breast cancer models at our institute 44,45
and
demonstrated both triggering of specific in vitro T cell reactivity and clinically
significant in vivo responses in animal models. MM-DC fusions used as vaccines
have similarly induced in vitro and in vivo specific responses in animal models; to
date, prophylactic MM-DC vaccinations have inhibited the subsequent ability to
induce MM in syngeneic mouse models; and in animals already bearing MM, MM-
DC vaccinations appear to prolong survival. Trials are now underway to test the
safety and efficacy of MM-DC vaccinations in humans. Finally, to facilitate these
and other novel immune approaches using DCs, we and others have shown that it
is possible to generate large numbers of DCs from both the BM and PB of patients
with MM which retain normal phenotype and APC function (Chauhan et al. and
Raje et al., manuscripts submitted). 46
- 47
This is true even though our studies suggest
that a fraction of these DCs contain human herpesvirus 8 gene sequences(Chauhan
et al. and Raje et al., manuscripts submitted). The stage is therefore set for
posttransplant immune-based treatments in patients with MM.
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