Generation of tumor-specific T-cell therapies

Morris, Emma; Hart, D.; Gao, Liquan; Tsallios, A; Xue, Shao-An; Stauss, Hans J.

doi:10.1016/j.blre.2005.05.001

Cited by 41 publications

(28 citation statements)

References 58 publications

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“…24 While examining the trafficking of effector cell population to other lymphoid organs because of CpG ODN, it was evident that the decrease in antigen-specific CD81 T cell response from the spleen is not due to the migration of anti-OVA CD81 T cells to lymph nodes following immunization in presence of CpG. Similarly, a lower number of antigenic CD81 T cells were observed in the blood from the Ad5-OVA1CpG immunized mice (unpublished data).…”

Section: Discussionmentioning

confidence: 95%

Paradoxical enhancement of CD8 T cell‐dependent anti‐tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine

Karan

Krieg

Lubaroff

2007

Intl Journal of Cancer

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Generation of antigen-specific CD81 T cell responses is considered optimal for an effective immunotherapy against cancer. In this study, we provide a proof of principle that in vitro observed diminished CD81 T cell response provided a strong in vivo tumor protection. Immunization with an adenovirus vaccine containing ovalbumin (OVA) gene (Ad5-OVA) strongly induces antigen-specific CD81 T cell responses measured in vitro using various immunological assays. However, in an attempt to augment the antigenic CD81 T cell response, coinjection of a TLR9 agonist CpG ODN with the viral vaccine unexpectedly reduced the CD81 T cell responses measured in vitro but provided a remarkably enhanced tumor protection compared to the CD81 T cell response generated by Ad5-OVA vaccine alone. Interestingly, despite reduced ex vivo/in vitro CD81 T cell responses following Ad5-OVA1CpG immunization, immunodepletion studies revealed that the augmented anti-tumor immunity was primarily dependent on CD81 T cells. The magnitude and effector function of anti-OVA CD81 T cells remain low following primary and secondary antigenic challenge, presenting a dichotomy between in vitro CD8 T cell responses and in vivo anti-tumor immunity. To examine the impact of CpG ODN, we observed that presence of CpG suppresses the CD81 T cell proliferation both in vitro and in vivo. These data demonstrate that coadministration of adenovirus vaccine with a TLR9 agonist can generate potentially effective tumorreactive CD81 T cells in vivo. In addition, the results indicate that widely used standard immune parameters may not predict the vaccine efficacy containing a TLR9 agonist as adjuvant. ' 2007 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Paradoxical enhancement of CD8 T cell‐dependent anti‐tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine

Karan

Krieg

Lubaroff

2007

Intl Journal of Cancer

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“…18,19 These observations encouraged the study of new strategies of immune therapy for hematological malignancies via infusions of T cells specific for tumor antigens, or via vaccination against leukemia-associated antigens (see the excellent review by Morris et al). 20 In addition to the progress made with cellular-based immunotherapy, advances in the field of tumor-targeting monoclonal antibodies (mAbs) have taken place in recent years, as illustrated by the development of chimeric mAbs targeting the CD20 antigen, which are now used in all types of B-cell non-Hodgkin lymphomas (NHLs) 21 , or CD52 or CD33 antigens, used increasingly for the treatment of chronic lymphocytic leukemia (CLL) 22 or acute myeloid leukemia (AML) 23,24 respectively. In addition, b-emitting radionuclides conjugated to mAb directed against the CD45 antigen (expressed on all U N C O R R E C T E D P R O O F hematopoietic cells) have been investigated as a way of increasing the anti-leukemic potency of conditioning regimens for HCTwithout inducing undue systemic toxicities.…”

Section: E17mentioning

confidence: 99%

“…93 By optimizing culture conditions it became possible to isolate from normal donors or from leukemia patients infrequent T cells which had cytotoxic activity against such tumor-associated antigens both in vitro and in xenotransplantation models. 20,94 Studies in the early 1990s showed that it was possible to restore T-cell immunity to cytomegalovirus (CMV) after allogeneic HCT by transfer of CMV-specific T cells. 95 Similar results were obtained with EBV as target.…”

Section: Tumor-associated Antigens and Transfer Of Tumor-specific T Cmentioning

confidence: 99%

“…20 These limitations might be overcome by recent approaches that have used genetic modifications of T cells, for example by transfer of genes coding for tumor-specific T-cell receptors with or without genes coding for signaling domains of co-stimulatory molecules (see excellent reviews by Morris et al and Rossig and Brenner). 20,97 Vaccination A recent review of vaccination trials performed in over 400 patients with solid cancer (mainly metastatic melanomas) showed an objective response rate of only 2.6%. 98 However, more encouraging results have been observed in patients with non-Hodgkin B-cell lymphoma (NHL) by targeting the tumor-specific Ig-Id, with 20e35% of patients achieving objective responses.…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

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The immune system as a foundation for immunologic therapy and hematologic malignancies: a historical perspective

Baron

Storb

2006

Best Practice & Research Clinical Haematology

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In this review we aim to provide a historical overview of the immunotherapeutic approaches which have been developed for the treatment of hematological malignancies. After briefly summarizing the development of the theory of cancer immune surveillance, we describe how initial studies discovering the efficacy of the immune-mediated graft-versus-tumor effects after allogeneic hematopoietic cell transplantation led to new transplantation approaches (termed non-myeloablative transplantation) relying almost exclusively on graft-versus-tumor effects for tumor eradication. We then summarize important steps in the development of tumor vaccines and autologous adoptive immunotherapy in patients with hematological malignancies. Finally, we describe historical discoveries leading to the recent success with monoclonal antibodies as treatment for lymphomas, chronic lymphocytic leukemia, and acute myeloid leukemia.

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“…Transducing TCR into CD4 + T cells also resulted in long-term tumor protection since CD4 + T cells produced high levels of IL-2 expanded in vivo, providing help for CTLs-mediated tumor rejection (125), which can be used for establishment of long-term tumor immunity (126).…”

Section: Tumor Adoptive Therapymentioning

confidence: 99%