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Allogeneic Stem Cell Transplantation and Other Immunotherapies for Pediatric Malignancies
Released: October 28, 2005
Presented: September 22, 2005

Abstract

There is now ample evidence that many pediatric malignancies express tumor-associated or tumor-specific antigens. These antigens may therefore be targets for immune- mediated cell destruction; and allogeneic stem cell transplantation takes advantage of this susceptibility. However, tumors that are potentially immunogenic usually develop evasion strategies that may passively shield the tumor or actively subvert the immune system. Pre-clinical and clinical studies have demonstrated a number of adoptive and active immunotherapy strategies that can overcome these evasion mechanisms. In addition, the ability to genetically manipulate components of the immune system has greatly increased the potential of these approaches.

We have studied the effects of immune modulation in children with leukemia, lymphoma, and neuroblastoma, treating some children soon after stem cell transplantation and others who have advanced disease. We have also adoptively transferred cytotoxic T cells active against EBV antigens into patients with Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, or nasopharyngeal carcinoma.

In addition, we have used active immunization with gene-modified autologous or allogeneic cell vaccines for children with leukemia or neuroblastoma. Both adoptive and active approaches produced anti-tumor immunity and resulted in sustained remissions, even in patients with advanced resistant disease. However, the majority of patients show incomplete or no response. It seems likely that truly effective immunotherapy will require a combination of both adoptive and active immunotherapy and incorporation of monoclonal antibodies to enhance immune responsiveness. We are now using such approaches in patients with Hodgkin’s Disease, lymphoma and nasopharyngeal carcinoma. Our early results with CD 45 MAb appear promising. Ultimately, the development of combination immunotherapies may have as great an impact on disease outcome as combination chemotherapy, but with considerably lower morbidity and mortality.



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About the presenter(s)

Malcolm K. Brenner, MD, PhD, FRCP, FRCPath

  • Last Updated: 30 Jul 2007

References


Please cite this seminar as:

Brenner, M. Allogeneic Stem Cell Transplantation and Other Immunotherapies for Pediatric Malignancies
Cure4Kids #802. Released on Cure4Kids: 28 Oct 2005.
URL: https://www.cure4kids.org/seminar/802/

This seminar's references:

Rossig C, Nuchtern JG, Brenner MK. Selection of human antitumor single-chain Fv antibodies from the B-cell repertoire of patients immunized against autologous neuroblastoma. Med Pediatr Oncol. 2000 Dec;35(6):692-5.
Abstract
Brenner MK, Heslop H, Krance R, Horowitz M, Strother D, Nuchtern J, Grilley B, Martingano E, Cooper K. Phase I study of chemokine and cytokine gene-modified autologous neuroblastoma cells for treatment of relapsed/refractory neuroblastoma using an adenoviral vector . Hum Gene Ther. 2000 Jul 1;11(10):1477-88.
Abstract
Brenner M. Adoptive therapy of posttransplant lymphoma . Cancer J. 2000 May;6 Suppl 3:S259-64.
Abstract
Kuehnle I, Huls MH, Liu Z, Semmelmann M, Krance RA, Brenner MK, Rooney CM, Heslop HE. CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation . Blood. 2000 Feb 15;95(4):1502-5.
Abstract
Rousseau RF, Hirschmann-Jax C, Takahashi S, Brenner MK. Cancer vaccines . Hematol Oncol Clin North Am. 2001 Aug;15(4):741-73.
Abstract
Savoldo B, Goss J, Liu Z, Huls MH, Doster S, Gee AP, Brenner MK, Heslop HE, Rooney CM. Generation of autologous Epstein-Barr virus-specific cytotoxic T cells for adoptive immunotherapy in solid organ transplant recipients. Transplantation. 2001 Sep 27;72(6):1078-86.
Abstract
Gahn B, Siller-Lopez F, Pirooz AD, Yvon E, Gottschalk S, Longnecker R, Brenner MK, Heslop HE, Aguilar-Cordova E, Rooney CM. Adenoviral gene transfer into dendritic cells efficiently amplifies the immune response to LMP2A antigen: a potential treatment strategy for Epstein-Barr virus--positive Hodgkin's lymphoma. Int J Cancer. 2001 Sep 1;93(5):706-13.
Abstract
Heslop HE, Bollard CM, Gottschalk S, Kuehnle I, Huls MH, Gee AP, Brenner MK, Rooney CM. Immune therapy for EBV infections after hemopoietic stem-cell transplant . Cytotherapy. 2002;4(5):433-4.
Abstract
Wulf GG, Luo KL, Goodell MA, Brenner MK. Anti-CD45-mediated cytoreduction to facilitate allogeneic stem cell transplantation . Blood. 2003 Mar 15;101(6):2434-9. Epub 2002 Nov 14.
Abstract
Rossig C, Bollard CM, Nuchtern JG, Rooney CM, Brenner MK. Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy . Blood. 2002 Mar 15;99(6):2009-16.
Abstract
Rossig C, Brenner MK. Chimeric T-cell receptors for the targeting of cancer cells . Acta Haematol. 2003;110(2-3):154-9.
Abstract
Brenner MK, Wulf GG, Rill DR, Luo KL, Goodell MA, Mei Z, Kuehnle I, Brown MP, Pule M, Heslop HE, Krance RA. Complement-fixing CD45 monoclonal antibodies to facilitate stem cell transplantation in mouse and man . Ann N Y Acad Sci. 2003 May;996:80-8.
Abstract
Rousseau RF, Haight AE, Hirschmann-Jax C, Yvon ES, Rill DR, Mei Z, Smith SC, Inman S, Cooper K, Alcoser P, Grilley B, Gee A, Popek E, Davidoff A, Bowman LC, Brenner MK, Strother D. Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with interleukin-2 in patients with advanced or refractory neuroblastoma . Blood. 2003 Mar 1;101(5):1718-26. Epub 2002 Oct 24.
Abstract
Rossig C, Brenner MK. Genetic modification of T lymphocytes for adoptive immunotherapy . Mol Ther. 2004 Jul;10(1):5-18.
Abstract
Rousseau RF, Brenner MK. Vaccine therapies for pediatric malignancies . Cancer J. 2005 Jul-Aug;11(4):331-9.
Abstract

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Seminar
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