A phase I trial for the treatment of purine analog-refractory chronic lymphocytic leukemia using autologous T cells genetically targeted to the B cell specific antigen CD19

Brentjens, R. J.; Hollyman, Daniel; Weiss, Michael; Stefanski, Jolanta; Przybylowski, Mark; Bartido, Shirley; Bórquez-Ojeda, Oriana; Taylor, Carolyn; Heaney, Mark L.; Rivière, Isabelle; Sadelain, Michel

doi:10.1200/jco.2008.26.15_suppl.3045

Cited by 4 publications

(3 citation statements)

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“…In the past year, two patients died on Phase I designer T cell studies: one targeting CD19 in lymphoma [ 24 , 25 ] and the other targeting Her2/neu in breast cancer [ 26 , 27 ]. Both were previously untested targets for designer T cells.…”

Section: Appendix 1: Designer T Cell Study Deathsmentioning

confidence: 99%

Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

Junghans

2010

J Transl Med

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Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs) for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

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Section: Appendix 1: Designer T Cell Study Deathsmentioning

confidence: 99%

Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

Junghans

2010

J Transl Med

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“…These have prompted a number of recent trials for lymphoma patients, the first of which, using the simpler construct of only scFv plus CD3δ, have been published [85] or presented [86], demonstrating safety, feasibility, moderate in vivo persistence and some clinical activity (TABLE 3). …”

Section: Adoptive Transfer Clinical Trialsmentioning

confidence: 99%

“…In addition, ongoing studies are exploring the above discussed possibility of using leukodepleting conditioning regimens prior to T-cell transfer. These have included cyclophosphamide-[86] and/or fludarabine-based regimens (ClinicalTrials.gov Identifier: NCT00182650) and have already given some indications of improved efficacy [SADELAIN M, PERS. COMM.…”

Section: Adoptive Transfer Clinical Trialsmentioning

confidence: 99%

Lymphoma Immunotherapy: Vaccines, Adoptive Cell Transfer and Immunotransplant

Brody

Levy

2009

Immunotherapy

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Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’.

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New approaches to allogeneic hematopoietic stem cell transplantation in pediatric cancers

Cooper

2009

Curr Oncol Rep

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A phase I trial for the treatment of purine analog-refractory chronic lymphocytic leukemia using autologous T cells genetically targeted to the B cell specific antigen CD19

Cited by 4 publications

References 0 publications

Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

Lymphoma Immunotherapy: Vaccines, Adoptive Cell Transfer and Immunotransplant

New approaches to allogeneic hematopoietic stem cell transplantation in pediatric cancers

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