Treatment of Metastatic Renal Cell Carcinoma With Autologous T-Lymphocytes Genetically Retargeted Against Carbonic Anhydrase IX: First Clinical Experience

Lamers, Cor H.J.; Sleijfer, Stefan; Vulto, Arnold G.; Kruit, Wim; Kliffen, Mike; Debets, Reno; Gratama, Jan W.; Stoter, G.; Oosterwijk, Egbert

doi:10.1200/jco.2006.05.9964

Cited by 813 publications

(704 citation statements)

References 8 publications

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“…This is reflected by the emergence of antigen-specific CD8 þ T cells in the peripheral blood of AML patients following transplantation. Such CTL responses have been reported against a broad range of AML-related tumor antigens, including HOXA9 (HOXA9 146-154 ), 62 hTERT (hTERT 540-548 ), 62 27,62 and RAGE-1 (RAGE-1 [11][12][13][14][15][16][17][18][19][20] (Table 1). 79 NuSAP1 has been identified as a target of humoral immunity following allogeneic HSCT.…”

Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 83%

“…For example, the TAA G250/carbonic anhydrase IX, which has also been identified as a LAA, is known to be expressed in the bile duct epithelium, accounting for the reported risk of developing cholestasis during G250-targeted T-cell therapy. 13 Nevertheless, the risk of autoimmunity with TAA-specific immunotherapy is generally considered to be theoretical because of the natural immunological tolerance towards self-antigens. In view of this, one can speculate whether TAAs could qualify as valid candidate targets for immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.

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Section: Criterion 4: Immunogenicity Humoral and Cellular Immune Respmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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“…[1][2][3][4] Patient-derived T cells are retrovirally engineered ex vivo to express a recombinant T-cell receptor or, alternatively, a chimeric antigen receptor (CAR, immunoreceptor), amplified and re-infused to recognize and to destroy tumour lesions by their cytolytic capacities. In contrast to recombinant T-cell receptors, CARs consist of a single polypeptide chain with an antibody-derived single chain fragment (scFv) in the extracellular moiety for binding and the CD3z or combined CD28-CD3z signalling domain in the intracellular moiety for T-cell activation.…”

Section: Introductionmentioning

confidence: 99%

Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

2010

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“…Recently, transfer of such second generation CAR T cells targeting CD19 + B cell lymphoid leukemia has shown encouraging clinical results in treating patients with bulky tumors (7)(8)(9)(10). Although these results are galvanizing the field of adoptive cell therapy, clinical trials focusing on solid tumors have seen less success (11)(12)(13). The challenge for T cell-based therapies of solid tumors lies in that T cells, in addition to reaching their targets, are required to survive and function within the unfavorable tumor microenvironment.…”

mentioning

confidence: 97%

Coexpressed Catalase Protects Chimeric Antigen Receptor–Redirected T Cells as well as Bystander Cells from Oxidative Stress–Induced Loss of Antitumor Activity

Ligtenberg

Mougiakakos

Mukhopadhyay

et al. 2016

The Journal of Immunology

179

111

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Treatment of cancer patients by adoptive T cell therapy has yielded promising results. In solid tumors, however, T cells encounter a hostile environment, in particular with increased inflammatory activity as a hallmark of the tumor milieu that goes along with abundant reactive oxygen species (ROS) that substantially impair antitumor activity. We present a strategy to render antitumor T cells more resilient toward ROS by coexpressing catalase along with a tumor specific chimeric Ag receptor (CAR) to increase their antioxidative capacity by metabolizing H2O2. In fact, T cells engineered with a bicistronic vector that concurrently expresses catalase, along with the CAR coexpressing catalase (CAR-CAT), performed superior over CAR T cells as they showed increased levels of intracellular catalase and had a reduced oxidative state with less ROS accumulation in both the basal state and upon activation while maintaining their antitumor activity despite high H2O2 levels. Moreover, CAR-CAT T cells exerted a substantial bystander protection of nontransfected immune effector cells as measured by CD3ζ chain expression in bystander T cells even in the presence of high H2O2 concentrations. Bystander NK cells, otherwise ROS sensitive, efficiently eliminate their K562 target cells under H2O2-induced oxidative stress when admixed with CAR-CAT T cells. This approach represents a novel means for protecting tumor-infiltrating cells from tumor-associated oxidative stress–mediated repression.

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Treatment of Metastatic Renal Cell Carcinoma With Autologous T-Lymphocytes Genetically Retargeted Against Carbonic Anhydrase IX: First Clinical Experience

Cited by 813 publications

References 8 publications

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Adoptive immunotherapy with genetically engineered T cells: modification of the IgG1 Fc ‘spacer’ domain in the extracellular moiety of chimeric antigen receptors avoids ‘off-target’ activation and unintended initiation of an innate immune response

Coexpressed Catalase Protects Chimeric Antigen Receptor–Redirected T Cells as well as Bystander Cells from Oxidative Stress–Induced Loss of Antitumor Activity

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