The combimation of stem cell transplantation and immunotherapy: Future potential

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In summary, a number of new immunotherapeutic strategies are being developed to take advantage of the reduced tumor burden that occurs following induction chemotherapy and stem cell transplantation. Novel strategies to accelerate hematopoietic reconstitution have become accepted and/or are rapidly being implemented. These include the use of PBSC's as compared to BM stem cells. PBSC's appear to accelerate hematopoietic reconstitution, have a lower likelihood of occult tumor cell contamination and contain a greater number of T cells in the product which may allow an accelerated immunologic reconstitution post transplantation. Similarly, the concept of GVT is no longer viewed as an epiphenomenon but following allotransplantation is an objectively supported and clinically important phenomena. Further, post transplantation adjunct therapy with a variety of immunoaugmenting agents may induce an autologous GVT response. Additional benefits of PBSCT beyond those associated with the accelerated hematopoietic reconstitution and concomitant tumor reduction is the reduced expense of a transplantation due to a shorter stay within the hospital. The isolation of stem cells (CD-34+) with or without ex vivo expansion to reduce the amount of stem cell product required is also an exciting new clinical strategy. This approach may also reduce the tumor cell contamination of the stem cell product, result in a more rapid hematologic reconstitution and reduce costs. However, it also has a potential down side due to a reduced infusion of mature and functional T cells. The comparison of PBSC to BM for transplantation of NHL suggests that the infusion of, or rapid reconstitution of, a functional immune system may have therapeutic benefit as discussed above. Thus, in addition to strategies based on the induction of an autologous GVT there is the need to develop/initiate clinic strategies to over come the immunosuppression-anergy associated with stem cell transplantation, as well as, augment tumor specific T cell responses to 'mop up' the residual tumor cells post transplantation. Clearly the clinical use of cytokines, especially in conjunction with PBSCT, has as a goal not only the reduction of morbidity and mortality associated with standard therapy but also dose intensification and scheduled compression so that increasing numbers of individuals may survive their current neoplasia. However, to date the use of the ex vivo expansion of stem and progenitor cells remains a largely unexplored clinical application for use in transplantation. The ex vivo expanded cells might also be useful for a variety of additional reasons: 1) From a practical standpoint the expansion of cells might be expected to reduce harvesting time and effort, 2) Decrease the infusion dose required for reconstitution following transplantation, 3) Allow the use of ex vivo expanded stem and progenitor cells from the peripheral blood in situations in which adequate numbers of BM cells might not be able to be harvested, and 4) Increased cell division during expansion which may improve the transduction efficacy of genetic material via recombinant retroviral vectors, a current limitation to the use of gene transfer technology for curative human somatic gene therapy. In theory, the use of ex vivo expansion might also be used to augment immune responses in vivo. For instance one could envision combining the purification of stem cells from contaminating tumor cells with their selective amplification ex vivo for autologous transplantation in settings which are now only amenable for allotransplantation. Further, with a better understanding of the cellular components of the postransplantation immune system we hope to be able to selectively amplify the cells responsible for GVT and/or expand specific cytotoxic effector T cell, for the treatment of neoplasia. In summary, we appear to be entering into an exciting new era whereby stem cell transplantation in combination with cytokine therapy, T cell expansion, and gene therapy maybe becoming a practical, cost effective therapeutic strategy.

Original languageEnglish (US)
Pages (from-to)675-690
Number of pages16
JournalIn Vivo
Issue number5
StatePublished - 1994


  • Bone marrow transplantation
  • Cord blood
  • IFN-α
  • IL-2
  • Immunotherapy
  • Peripheral blood stem cell
  • Stem cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology


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