Abstracts of 4th Annual UKMF Scientific Meeting on 07-Feb-2003
Prospects for adoptive T cell therapy of multiple myeloma
Paul Moss, University of Birmingham
There is increasing optimism about the prospects for immunotherapy of myeloma. A number of potential tumour-associated antigens (TAA) have been described and our ability to manipulate specific arms of the immune system both in vitro and in vivo increase steadily. However, there remain many issues to be overcome before immunotherapy is likely to prove of substantial benefit in the autologous setting.
Status of baseline immune response to TAA
It is not clear to what extent immune responses exist to current potential
TAA such as idiotype or cancer testis antigens (CTA). Humoral immunity
to idiotype has been documented and although cellular responses have
been documented by Elispot analysis, well characterized TAA-specific
T cell clones are rarely isolated from patients. This information is
important because it is not certain whether or not investigators will
need to generate primary immune responses, overcome anergic reactivity
or boost effective, but quantitatively or qualitatively weak, ongoing
immunity. The baseline level of immune responsiveness of myeloma patients
must also been taken into consideration.
Approaches to immunotherapy
Vaccination or adoptive cellular therapy are the major therapeutic developments
in immune therapy of cancer. Vaccination may be performed using a variety
of approaches and these are being tested in many clinical contexts. The
paucity of adjuvants limits the value of protein vaccines in man but
DNA vaccination offers great hope.
With cellular therapy, most attention has been given to dendritic cell therapy and a number of trials are in progress in patients with a variety of malignancies. Encouraging responses have been observed but the optimal approach to dendritic cell vaccination remains unclear.
Adoptive T cell therapy has not been widely developed in the treatment of human cancer, largely because of the difficulty in obtaining high avidity tumour-reactive T cells in vitro. However, such approaches are relatively well developed in the therapy of viral disease, particularly in the allogeneic transplant setting.
We have recently been using an adoptive T cell transfer approach that relies on the purification of effector T cells from immune transplant donors followed by their direct infusion into transplant recipients. The lessons that may be applied from this work to the development of adoptive T cell transfer in multiple myeloma will be discussed.