The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
J.M. Bull - One of the best experts on this subject based on the ideXlab platform.
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A review of immune therapy in cancer and a question: can thermal therapy increase tumor response?
International Journal of Hyperthermia, 2017Co-Authors: J.M. BullAbstract:Immune therapy is a successful cancer treatment coming into its own. This is because checkpoint molecules, adoptive specific Lymphocyte Transfer and chimeric antigen T-cell (CAR-T) therapy are able...
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A Review of Immune Therapy in Cancer and a Question: Can Thermal Therapy Increase Tumor Response?
International Journal of Hyperthermia, 2017Co-Authors: J.M. BullAbstract:AbstractImmune therapy is a successful cancer treatment coming into its own. This is because checkpoint molecules, adoptive specific Lymphocyte Transfer, and CAR-T therapy are able to induce more responses and more durable responses in an increasing number of malignancies compared to chemotherapy. In addition, immune therapies are able to treat bulky disease, whereas standard cytotoxic therapies cannot treat large tumor burdens. Checkpoint inhibitor monoclonal antibodies are becoming widely used in the clinic; and although more complex, adoptive Lymphocyte Transfer and CAR-T therapies show promise. We are learning that there are nuances to predicting the successful use of the checkpoint inhibitors as well as to specific-antigen adoptive and CAR-T therapies. We are also newly aware of a here-to-fore unrealized natural force, the status of the microbiome. However, despite better understanding of mechanisms of action of the new immune therapies, the best responses to the new immune therapies remain 20-30%. L...
Steven A Rosenberg - One of the best experts on this subject based on the ideXlab platform.
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simultaneous targeting of tumor antigens and the tumor vasculature using t Lymphocyte Transfer synergize to induce regression of established tumors in mice
Cancer Research, 2013Co-Authors: Dhanalakshmi Chinnasamy, Eric Tran, Zhiya Yu, Richard A Morgan, Nicholas P Restifo, Steven A RosenbergAbstract:Most systemic cancer therapies target tumor cells directly though there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous Transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2; KDR) that is over expressed on tumor vasculature and T cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared to treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion prior to cell Transfer was required to mediate the anti-tumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively Transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their anti-tumor potency. The data presented here emphasize the possible beneficial effects of combining anti-angiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer.
Dhanalakshmi Chinnasamy - One of the best experts on this subject based on the ideXlab platform.
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simultaneous targeting of tumor antigens and the tumor vasculature using t Lymphocyte Transfer synergize to induce regression of established tumors in mice
Cancer Research, 2013Co-Authors: Dhanalakshmi Chinnasamy, Eric Tran, Zhiya Yu, Richard A Morgan, Nicholas P Restifo, Steven A RosenbergAbstract:Most systemic cancer therapies target tumor cells directly though there is increasing interest in targeting the tumor stroma that can comprise a substantial portion of the tumor mass. We report here a synergy between two T cell therapies, one directed against the stromal tumor vasculature and the other directed against antigens expressed on the tumor cell. Simultaneous Transfer of genetically engineered syngeneic T cells expressing a chimeric antigen receptor targeting the Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2; KDR) that is over expressed on tumor vasculature and T cells specific for the tumor antigens gp100 (PMEL), TRP-1 (TYRP1), or TRP-2 (DCT) synergistically eradicated established B16 melanoma tumors in mice and dramatically increased the tumor-free survival of mice compared to treatment with either cell type alone or T cells coexpressing these two targeting molecules. Host lymphodepletion prior to cell Transfer was required to mediate the anti-tumor effect. The synergistic antitumor response was accompanied by a significant increase in the infiltration and expansion and/or persistence of the adoptively Transferred tumor antigen-specific T cells in the tumor microenvironment and thus enhanced their anti-tumor potency. The data presented here emphasize the possible beneficial effects of combining anti-angiogenic with tumor-specific immunotherapeutic approaches for the treatment of patients with cancer.
Dorothee Herlyn - One of the best experts on this subject based on the ideXlab platform.
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Combination of active specific immunotherapy or adoptive antibody or Lymphocyte immunotherapy with chemotherapy in the treatment of cancer
Cancer Immunology Immunotherapy, 2009Co-Authors: Tianqian Zhang, Dorothee HerlynAbstract:Successful treatment of cancer patients with a combination of monoclonal antibodies (mAb) and chemotherapeutic drugs has spawned various other forms of additional combination therapies, including vaccines or adoptive Lymphocyte Transfer combined with chemotherapeutics. These therapies were effective against established tumors in animal models and showed promising results in initial clinical trials in cancer patients, awaiting testing in larger randomized controlled studies. Although combination between immunotherapy and chemotherapy has long been viewed as incompatible as chemotherapy, especially in high doses meant to increase anti-tumor efficacy, has induced immunosuppression, various mechanisms may explain the reported synergistic effects of the two types of therapies. Thus direct effects of chemotherapy on tumor or host environment, such as induction of tumor cell death, elimination of regulatory T cells, and/or enhancement of tumor cell sensitivity to lysis by CTL may account for enhancement of immunotherapy by chemotherapy. Furthermore, induction of lymphopenia by chemotherapy has increased the efficacy of adoptive Lymphocyte Transfer in cancer patients. On the other hand, immunotherapy may directly modulate the tumor’s sensitivity to chemotherapy. Thus, anti-tumor mAb can increase the sensitivity of tumor cells to chemotherapeutic drugs and patients treated first with immunotherapy followed by chemotherapy showed higher clinical response rates than patients that had received chemotherapy alone. In conclusion, combination of active specific immunotherapy or adoptive mAb or Lymphocyte immunotherapy with chemotherapy has great potential for the treatment of cancer patients which needs to be confirmed in larger controlled and randomized Phase III trials.
D. L. Dunn - One of the best experts on this subject based on the ideXlab platform.
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Relevance of tumor necrosis factor to graft-versus-host disease after small bowel transplantation
Transplant International, 1993Co-Authors: J. Pirenne, M. D'silva, G. Degiovanni, N. Jacquet, D. L. DunnAbstract:The small bowel (SB), an organ replete with Lymphocytes, may provoke graft-versus-host disease (GVHD) after transplantation (Tx). Since tumor necrosis factor (TNF) has been suspected of mediating the tissue lesions of GVHD, we sought to determine whether TNF could be detected in the serum of rats undergoing GVHD after SBTx or Lymphocyte Transfer. For this purpose, post-operative serum TNF activity was determined in Lewis x Brown after undergoing transplantation of an entire (group 1; n =8) or a segmental (group 2; n =4) Lew SB, or after i. p. injection with lethal doses (500×10^6) of Lew Lymphocytes (group 3; n =3). Control LBNF1 received i.p. small doses (50×10^6) of Lew Lymphocytes (group 4; n =4). Serum TNF activity was assessed using the WEHI bioassay. In rats with acute and lethal GVHD after entire SBTx (group 1) or injection with large doses of Lymphocytes (group 3), TNF activity gradually increased and reached high levels by the time the rats were agonal. In segmental SBTx rats (group 2), GVHD was less severe than in entire SBTx rats. Similarly, the increase in TNF activity was less intense and only transient since it had returned to control levels by the time the rats had completely recovered from GVHD. In control rats primed with small doses of Lymphocytes (group 4), GVHD did not occur and no increase in TNF activity was detected. We conclude that: (1) GVHD after SBTx or Lymphocyte Transfer is associated with the appearance of TNF in the serum and (2) the intensity and the reversibility of this phenomenon correlate with clinical severity and lethality of GVHD. These data strongly suggest that TNF is involved in the pathogenesis of GVHD.
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Mechanisms of graft versus host disease produced by small bowel transplantation
Acta Chirurgica Austriaca, 1991Co-Authors: J. P. Pirenne, G. Degiovanni, D. L. DunnAbstract:Mechanisms of graft versus host disease have been studied in Lew x BN animals transplanted with a Lew small bowel. Grafted mesenteric lymph nodes but not host mesenteric lymph nodes or host spleen, in small bowel transplanted rats undergoing lethal GVHD, provide a source of CTL with specific anti-recipient cytotoxic activity. Host MLN and host spleen display anti-recipient CTL activity only when GVHD is provoked by intraperitoneal Lymphocyte injection. These data demonstrate that lethal GVHD after SBTx may occur in the absence of detectable cytotoxic activity in host lymphoid tissues, suggesting that other mechanisms are involved in the pathogenesis of GVHD after SBTx. GVHD after SBTx or Lymphocyte Transfer is associated with the appearance of TNF in the serum. The intensity and reversibility of this phenomenon correlate with both the clinical severity and the lethality of GVHD. Taken together these data highly suggest that TNF is directly involved in the pathogenesis of GVHD after SBTx.
