Journal Mobile Options
Table of Contents
Vol. 105, No. 3, 2001
Issue release date: July 2001
Acta Haematol 2001;105:130–136

Activated T-Cell and Bispecific Antibody Immunotherapy for High-Risk Breast Cancer

Bench to Bedside

Lum L.G. · Sen M.
Roger Williams Cancer Center, Providence, R.I., and Blood Center of Southeast Wisconsin, Milwaukee, Wisc., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Nontoxic approaches are needed to improve overall survival (OS) and progression-free survival (PFS) for high-risk breast cancer. Combination immunotherapy (IT) consisting of activated T cells (ATC), interleukin-2 (IL-2), and CTL (GM-CSF) was given after peripheral blood stem cell transplant (PBSCT). There were no major toxicities and there appear to be improvements in OS and PFS over historical controls. In order to develop specific cytotoxic T lymphocytes (CTL), we combined ATC with the use of bispecific antibody (BiAb). By arming ATC with anti-CD3 × anti-HER2/neu BiAb (HER2BiAb), the approach converts nonspecific ATC into HER2/neu (HER2) specific CTL. ATC remain armed, kill tumor targets for days, and produce cytokines after binding to tumor. Arming ATC with BiAbs may prove to be effective for targeting a variety of tumors with and without high-dose chemotherapy.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Paterson AHG, Lees AW, Hanson J, Szafra O, Cornish F: Impact of chemotherapy on survival in metastatic breast cancer. Lancet 1980;ii:312.
  2. Fey MF, Brunner KW, Sontag RW: Prognostic factors in metastatic breast cancer. Cancer Clin Trials 1981;4:237–247.

    External Resources

  3. Nemoto J, Vana J, Bedwani RN: Management and survival of female breast cancer: Results of a national survey by the American College of Surgeons. Cancer 1980;45:2917.
  4. Carter CL, Allen C, Henson DE: Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989;63:181–187.
  5. Van Wauwe JP, De Mey JR, Gooseens JG: OKT3: A monoclonal anti-human T lymphocyte antibody with potent mitogenic properties. J Immunol 1980;124:2708–2713.
  6. Meuer SC, Hodgdon JC, Hussey RE, Protentis JP, Schlossman SF, Reinherz EL: Antigen-like effects of monoclonal antibodies directed at receptors on human T cell clones. J Exp Med 1983;158:988–993.
  7. Weiss A, Imboden JB: Cell surface molecules and early events involved in human T lymphocyte activation. Adv Immunol 1987;41:1–38.

    External Resources

  8. Ochoa AC, Gromo G, Alter BJ, Sondel PM, Bach FH: Long-term growth of lymphokine- activated killer (LAK) cell: Role of anti-CD3, beta-IL 1, interferon-gamma and -beta. J Immunol 1987;138:2728–2733.
  9. Anderson PM, Bach FH, Ochoa AC: Augmentation of cell number and LAK activity in peripheral blood mononuclear cells activated with anti-CD3 and interleukin-2. Preliminary results in children with acute lymphocytic leukemia and neuroblastoma. Cancer Immunol Immunother 1988;27:82–88.
  10. Yang SC, Fry KD, Grimm EA, Roth JA: Successful combination immunotherapy for the generation in vivo of antitumor activity with anti-CD3, interleukin 2, and tumor necrosis factor alpha. Arch Surg 1990;125:220–225.
  11. Ueda M, Joshi ID, Dan M, Uberti JP, Chou T-H, Sensenbrenner LL, Lum LG: Preclinical studies for adoptive immunotherapy in bone marrow transplantation. II. Generation of anti-CD3 activated cytotoxic T cells from normal donors and autologous bone marrow transplant candidates. Transplantation 1993;56:351–356.

    External Resources

  12. Uberti JP, Joshi I, Ueda M, Martilotti F, Sensenbrenner LL, Lum LG: Preclinical studies using immobilized OKT3 to activate human T cells for adoptive immunotherapy: Optimal conditions for the proliferation and induction of non-MHC restricted cytotoxicity. Clin Immunol Immunopathol 1994;70:234–240.
  13. Anderson PM, Blazar BR, Bach FH, Ochoa AC: Anti-CD3 + IL-2-stimulated murine killer cells: In vitro generation and in vivo antitumor activity. J Immunol 1989;142:1383–1394.
  14. Ting C-C, Hargrove ME, Yun YS: Augmentation by anti-T3 antibody of the lymphokine-activated killer cell-mediated cytotoxicity. J Immunol 1988;141:741–748.

    External Resources

  15. Sosman JA, Oettel KR, Hank JA, Fisch P, Sondel PM: Specific recognition of human leukemic cells by allogeneic T cell lines. Transplantation 1989;48:486.
  16. Katsanis E, Xu Z, Anderson PM, Dancisak BB, Bausero MA, Weisdorf DJ, Blazar BR, Ochoa AC: Short-term ex vivo activation of splenocytes with anti-CD3 plus IL-2 and infusion post-BMT into mice: Results in in vivo expansion of effector cells with potent anti-lymphoma activity. Bone Marrow Transplant 1994;14:563–572.
  17. Curti BC, Longo DL, Ochoa AC, Conlon KC, Smith JW, II, Alvord WG, Creekmore SP, Fenton RG, Gause BL, Holmlund J, Janik JE, Ochoa J, Rice PA, Sharfman WH, Sznol M, Urba WJ: Treatment of cancer patients with ex vivo anti-CD3-activated killer cells and interleukin-2. J Clin Oncol 1993;11:652–660.
  18. Curti BD, Ochoa AC, Powers GC, Kopp WC, Alvord WG, Janik JE, Gause BL, Dunn B, Kopreski MS, Fenton R, Zea A, Dansky-Ullmann C, Strobl S, Harvey L, Nelson E, Sznol M, Longo DL: Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer. J Clin Oncol 1998;16:2752–2760.

    External Resources

  19. Disis ML, Cheever MA: Her-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Adv Cancer Res 1997;71:343–371.
  20. Watanabe M, Nakada T, Yuta H: Analysis of protooncogene c-erbB-2 in benign and malignant human prostate. Int Urol Nephrol 1999;31:61–73.
  21. Schwartz S Jr, Caceres C, Morote J, de Torres I, Rodriguez-Vallejo JM, Gonzalez J, Reventos J: Gains of the relative genomic content of erbB-1 and erbB-2 in prostate carcinoma and their association with metastasis. Int J Oncol 1999;14:367–371.

    External Resources

  22. Morote J, de Torres I, Caceres C, Vallejo C, Schwartz S Jr, Reventos J: Prognostic value of immunohistochemical expression of the c-erbB-2 oncoprotein in metastasic prostate cancer. Int J Cancer 1999;84:421–425.
  23. Ullrich A, Schlessinger J: Signal transduction by receptors with tyrosine kinase activity. Cell 1990;61:203–212.
  24. Stockmeyer B, Valerius T, Repp R, Heijnen IAFM, Bühring H-J, Deo YM, Kalden JR, Gramatzki M, van de Winkel JGJ: Preclinical studies with Fc(gamma)R bispecific antibodies and granulocyte colony-stimulating factor-primed neutrophils as effector cells against Her-2/neu overexpressing breast cancer. Cancer Res 1997;57:696–701.

    External Resources

  25. Lamers CHJ, van de Griend RJ, Braakman E, Ronteltap CPM, Bernard J, Stoter G: Optimization of culture conditions for activation and large-scale expansion of human T lymphocytes for bispecific antibody-directed cellular immunotherapy. Int J Cancer 1992;51:973–979.
  26. Ogawa M, Yu W-G, Umehara K, Iwasaki M, Wijesuriya R, Tsujimura T, Kubo T, Fujiwara H, Hamaoka T: Multiple roles of interferon-gamma in the mediation of interleukin 12-induced tumor regression. Cancer Res 1998;58:2426–2432.
  27. Quian J-H, Titus JA, Andrew SM, Mezzanzanica D, Garrido MA, Wunderlich JR, Segal DM: Human peripheral blood lymphocytes targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth. J Immunol 1991;146:3250–2356.

    External Resources

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50