Specific Lysis of Melanoma Cells by Receptor Grafted T Cells is Enhanced by Anti-Idiotypic Monoclonal Antibodies Directed to the scFv Domain of the Receptor

Reinhold, Uwe; Tilgen, Wolfgang; Liu, Lide; Lüdtke-Handjery, Hans-Christian; Heuser, Claudia; Hombach, Andreas; Wang, Xinhui; Ferrone, Soldano; Abken, Hinrich

doi:10.1046/j.1523-1747.1999.00586.x

Cited by 25 publications

(15 citation statements)

References 29 publications

(32 reference statements)

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“…These cells, which are specific to the same non-MHC and restricted antigen, are capable of working in concert upon stimulation by their predefined target. A large repertoire of CRs that can selectively recognize different tumor-associated antigens has been constructed (10,(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) and in practice one can attack a given tumor with a panel of T bodies including several different specificities and CR designs. This arsenal should offer a workable solution to one of the major drawbacks of cancer immunotherapy: the regrowth of escape variants as a result of selective immunological pressure (7,40,41).…”

Section: Discussionmentioning

confidence: 99%

Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes

Pinthus

Waks²,

Malina³

et al. 2004

J. Clin. Invest.

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Prostate cancer is currently the most commonly diagnosed noncutaneous malignancy in American men. When metastatic, usually to the bone, the disease is no longer curable and is usually treated palliatively with androgen ablation. However, after conversion to androgen-independent disease, there is no effective therapy currently available. The "T body" approach, which uses genetically reprogrammed lymphocytes derived from the patient and expressing chimeric receptor genes, combines the effector functions of T lymphocytes and NK cells with the ability of antibodies to recognize predefined surface antigens with high specificity and in a non-MHC-restricted manner. We show here the therapeutic efficacy of human lymphocytes bearing erbB2-specific chimeric receptors on human prostate cancer BM lesions in a SCID mouse model after conditioning of the recipient to allow homing and persistent functioning of the adoptively transferred cells. Induction of stromal cell-derived factor-1 production within the BM using low-dose irradiation or cyclophosphamide combined with IL-2 administration enhanced the homing of systemically delivered T bodies, resulting in decreased tumor growth and prostate-specific antigen secretion, prolongation of survival, and even cure of the treated mice. These preclinical studies strongly support the idea that the T body approach has therapeutic potential in disseminated prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes

Pinthus

Waks²,

Malina³

et al. 2004

J. Clin. Invest.

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“…Effector cells transfected with the respective chimeric receptor have been shown to acquire the ability to lyse TAApositive tumor cells in a MHC-unrestricted fashion (review: Abken et al 1998). Recently, an anti-melanoma chimeric receptor was constructed in our laboratory and shown to be effective in mediating cytolysis melanoma cells in vitro (Reinhold et al 1999). …”

Section: The Chimeric T Cell Receptor Designmentioning

confidence: 99%

“…We constructed a recombinant TCR displaying both binding specificity for the high-molecular-weight-melanoma-associated antigen (HMW-MAA) and cellular activation after receptor cross-linking (Reinhold et al 1999). The extracellular antigen-binding domain consists of a scFv derived from an HMW-MAAspecific monoclonal antibody, 763.74.…”

Section: The Anti-melanoma Chimeric T Cell Receptormentioning

confidence: 99%

“…To facilitate enrichment by panning of recombinant phages that express scFv with specificity to membrane-bound antigens, we used anti-idiotypic monoclonal antibodies instead of isolated antigen (Hombach et al 1998b). By this procedure, we derived a scFv from the parental monoclonal antibody (mAb) 763.74 with specificity to the HMW-MAA (Reinhold et al 1999). The scFv 763.74 has retained binding specificity, as it displays specific reactivity in ELISA with a protein extract from HMW-MAA-positive melanoma cells, stains specifically antigen-positive melanoma cells, and is competed by the parental mAb in binding to melanoma cells.…”

Section: The Anti-melanoma Chimeric T Cell Receptormentioning

confidence: 99%

“…If so, will anti-idiotypic antibodies activate CTLs by costimulation or will they inhibit activation and homing of transduced T cells to malignant lesions? In vitro experiments suggest the two conflicting possibilities: addition of anti-idiotypic antibodies to mixtures of grafted CTLs and target cells inhibits lysis of target cells, but cross-linking of the receptor by immobilized anti-idiotypic antibodies enhances their lytic activity (Reinhold et al 1999). 7.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Strategy in the Elimination of Disseminated Melanoma Cells: Chimeric Receptors Endow T Cells with Tumor Specificity

Abken

Hombach

Heuser

et al. 2001

Minimal Residual Disease in Melanoma

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The application of immunotherapy to the treatment of micrometastases of melanoma has attracted growing interest in recent years. This trend reflects, at least in part, the disappointing results of conventional chemotherapy, the identification of melanoma-associated antigens suitable to be used as targets for immunotherapy, and the significant progress in our understanding of molecular processes involved in the development of an immune response. Because of the general belief that T cell immunity plays a major part in the control of tumor growth, we have recently applied a novel strategy to target cytolytic T cells to melanoma cells. The strategy bypasses the requirement of presentation of melanoma-associated-antigen-derived peptides by the major histocompatibility complex to the T cell receptor complex by permanent grafting of T cells with a recombinant, chimeric T cell receptor. The extracellular moiety of the grafted receptor contains the antigen-binding domain, consisting of a single-chain antibody fragment (scFv) derived from a monoclonal antibody specific for the high-molecular-weight melanoma-associated antigen (HMW-MAA). The intracellular receptor moiety contains the cellular activation domain, consisting of the y-signaling chain derived from the FceRI receptor. Cytotoxic T cells grafted with the chimeric anti-HMW-MAA scFv-y signaling receptor specifically lyse HMW-MAA-positive melanoma cells in a human leukocyte antigen class I-independent fashion. The chimeric T cell receptor strategy is designed to eliminate disseminated tumor cells by the power of cytolytic T cells that physiologically penetrate tissues and that are specifically activated by the grafted receptor after binding to antigen-positive melanoma cells.

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Emerging Therapeutic Concepts III: Chimeric Immunoglobulin T Cell Receptors, T‐Bodies

Schirrmann¹,

Pecher²

2007

Handbook of Therapeutic Antibodies

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Specific Lysis of Melanoma Cells by Receptor Grafted T Cells is Enhanced by Anti-Idiotypic Monoclonal Antibodies Directed to the scFv Domain of the Receptor

Cited by 25 publications

References 29 publications

Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes

Adoptive immunotherapy of prostate cancer bone lesions using redirected effector lymphocytes

A Novel Strategy in the Elimination of Disseminated Melanoma Cells: Chimeric Receptors Endow T Cells with Tumor Specificity

Emerging Therapeutic Concepts III: Chimeric Immunoglobulin T Cell Receptors, T‐Bodies

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