Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia

O’Hear, Carol; Heiber, Joshua F.; Schubert, Ingo; Fey, Georg H.; Geiger, Terrence L.

doi:10.3324/haematol.2014.112748

Cited by 86 publications

(53 citation statements)

References 47 publications

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“…Tumors that reached an approximate size <1,000 mm 3 were removed and passaged to other NSI mice. On days 7 and 10, according to the doses used in other reports, 53,54 5 £ 10 6 total T cells were injected through the tail vein into each NSCLC-burdened NSI mouse. Tumors were measured every 4 d with a caliper to determine the subcutaneous growth rate.…”

Section: Pdx Models For Car T Cell Treatmentmentioning

confidence: 99%

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

et al. 2017

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Section: Pdx Models For Car T Cell Treatmentmentioning

confidence: 99%

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

et al. 2017

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“…3,4 Several investigators have attempted to mimic the effects of HSCT without actually performing the transplant using cytokines, interferons, genetically engineered chimeric antigen receptor T cells, and various vaccines. [5][6][7] We have previously reported the results from a pilot study investigating the potential application of a multivalent heteroclitic Wilms tumor 1 (WT1) peptide vaccine (galinpepimut-S [GPS]) in the treatment of adult AML patients. 8 The heteroclitic peptides within the vaccine bear a single amino acid substitution in key residues that are specifically designed to both enhance antigenicity against and mitigate immune tolerance toward the corresponding native WT1 peptide sequences expressed in tumor cells and recognized by the host's immune system.…”

Section: Introductionmentioning

confidence: 99%

Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia

et al. 2018

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“…87 Although alternative antigens are explored, 88,89 current efforts focus primarily on CD33 and CD123. [90][91][92][93][94][95] Clinical trials testing CAR T cells directed at each of these antigens are ongoing, with one early report available of a patient who had a transient decrease in marrow blasts after receiving CD33-directed CAR T cells. 96 Less explored are T cells expressing modified TCR genes.…”

Section: Adoptive Immunotherapymentioning

confidence: 99%

Antigen-specific immunotherapies for acute myeloid leukemia

Buckley

Walter

2015

Hematology

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Antigen-specific immunotherapies have emerged as important components of curative treatment algorithms for many cancers. In acute myeloid leukemia (AML), success has been less obvious. Nonetheless, among the few drugs shown to improve survival in recent randomized trials is the CD33 antibody-drug conjugate gemtuzumab ozogamicin. Significant antileukemic activity is also well documented for radioimmunoconjugates targeting CD33, CD45, or CD66. These therapeutics can intensify conditioning before hematopoietic cell transplantation, but their effect on patient outcomes needs clarification. Emerging data now suggest clinical antileukemic activity of several novel antibodies and perhaps some adoptive T-cell immunotherapies and vaccines. In parallel, numerous other agents targeting a wider variety of antigens are currently being explored. However, the antigenic heterogeneity characteristic of AML is a considerable limitation for all these therapeutics, and many important questions related to the ideal target antigen(s), disease situation in which to use these therapies, most suitable patient populations, exact treatment modalities, and details of supportive care needs remain open. Addressing such questions in upcoming studies will be required to ensure that antigen-directed therapies become an effective tool in AML, a disease for which outcomes with standard "3 ϩ 7"-based chemotherapy have remained unsatisfactory in many patients. Learning Objectives• To gain an overview of current clinical results with antigenspecific immunotherapies for acute myeloid leukemia • To become familiar with recent advances and evolving treatment concepts in the field of antigen-specific immunotherapy for acute myeloid leukemia and to appreciate the challenges in the clinical translation of these therapeutic strategies Conceptually, antigen-specific immunotherapies offer a versatile means of eliminating tumor cells with limited nonspecific toxicities. For many human cancers, including some hematological malignancies, such therapies have emerged as important components of curative treatment algorithms. 1-3 Success has been more modest for acute myeloid leukemia (AML). Nonetheless, among the few drugs that have shown to improve survival in recent randomized trials is the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO). The clinical experience with GO provides the strongest glimpse thus far of the potential value of antigen-targeted therapies for AML. Here, we review the results of efforts with antibodies and other antigen-directed passive and active immunotherapies in AML and summarize evolving treatment strategies for this disease.

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Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia

Cited by 86 publications

References 47 publications

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia

Antigen-specific immunotherapies for acute myeloid leukemia

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