Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients

Fontana, Raffaella; Bregni, Marco; Cipponi, Arcadi; Raccosta, Laura; Rainelli, Cristina; Maggioni, Daniela; Lunghi, Francesca; Ciceri, Fabio; Mukenge, Sylvain; Doglioni, Claudio; Colau, Didier; Coulie, Pierre G.; Bordignon, Claudio; Traversari, Catia; Russo, Vincenzo

doi:10.1182/blood-2008-07-168666

Cited by 45 publications

(49 citation statements)

References 31 publications

(51 reference statements)

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“…In addition, we showed that these anti-CAR T-cell immune responses were directed against both the CAIX CAR transgene and potentially retroviral vector-encoded epitopes expressed by the CAR-engineered T cells. This study extends on previous observations on immunogenicity of transgenes, such as tumor associated antigens, suicide genes, and selection markers, [11][12][13][14]35 but is the first to document the clinical immunogenicity of both CARs and potentially retroviral vector-derived epitiopes.…”

Section: Discussionsupporting

confidence: 80%

“…[11][12][13][14]35 The sudden disappearance of circulating CAR T cells in patient 5 at day 36, without measurable levels of HACA, strongly suggested the existence of anti-CAR T-cell CMI. However, no such reactivity could be detected in fresh PBMCs taken from patients before, during, and after CAR T-cell therapy.…”

Section: Discussionmentioning

confidence: 93%

“…In immunecompetent hosts, the adoptive transfer of gene-modified immune effector cells may induce immune responses against the transgene, [11][12][13][14] resulting in limited persistence and hence limited antitumor effects of transferred gene-modified cells. 1,3 In addition, upon retroviral transduction, residual vector sequences that are integrated in the host cell genome theoretically might result in expression of immunogenic epitopes, which might further compromise their peripheral persistence.…”

Section: Introductionmentioning

confidence: 99%

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Immune responses to transgene and retroviral vector in patients treated with ex vivo–engineered T cells

Lamers

Willemsen

Elzakker

et al. 2011

Blood

319

308

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Adoptive transfer of immune effector cells that are gene modified by retroviral transduction to express tumor-specific receptors constitutes an attractive approach to treat cancer. In patients with metastatic renal cell carcinoma, we performed a study with autologous T cells genetically retargeted with a chimeric antibody receptor (CAR) directed toward carbonic anhydrase IX (CAIX), an antigen highly expressed in renal cell carcinoma. In the majority of patients, we observed distinct humoral and/or cellular anti-CAIX-CAR

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immune responses to transgene and retroviral vector in patients treated with ex vivo–engineered T cells

Lamers

Willemsen

Elzakker

et al. 2011

Blood

319

308

View full text Add to dashboard Cite

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“…Three out of 10 patients showed an increase in circulating anti-MAGE-A3 T cells, indicating a possible clinical benefit. No toxicity or adverse side effects were observed (Fontana et al 2009).…”

Section: Melanomamentioning

confidence: 91%

Gene Therapy for Skin Diseases

Gorell

Ngôn

Lane

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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“…[4][5][6] Alternatively, autologous lymphocytes were genetically modified to express antitumor αβ T-cell receptors (TCRs) to obtain large numbers of antitumor CTLs. 7,8 Clinical studies using the above strategies have demonstrated encouraging results in the treatment of tumors expressing defined tumor antigens. However, wide-spread application of tumor-specific αβ T-cell-based therapy may be hindered by its inherent limitations.…”

Section: Introductionmentioning

confidence: 99%

Adoptive immunotherapy of lung cancer with immobilized anti-TCRγδ antibody-expanded human γδ T Cells in peripheral blood

Kang¹,

Zhou²,

Tie³

et al. 2009

Cancer Biology & Therapy

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Lung cancer is the leading cause of cancer death. The prognosis of metastatic lung cancer is poor. We had previously established the condition to expand human γδ T-cells in peripheral blood and tumor infiltrating T lymphocytes with immobilized anti-TCRγδ antibody. Such expanded γδ T-cells exhibited potent cytolytic activity to different tumor cell lines in vitro and in vivo. Here we further characterized human anti-TCRγδ-expanded γδ T-cells and tested their antitumor function in treatment for lung cancer in nude mice. In comparison to γδ T-cells activated by phosphoantigen, a prevalent Vδ2 stimulus, anti-TCRγδ-expanded γδ T-cells had similar major subset with Vδ2 phenotype, but they had about 10% of Vδ1 subsets and high percentages of CD27 -CD45RA -and CD27 -CD45RA + effector cells. They also displayed TCR diversity of multiple clones. Importantly, the antibody-expanded γδ T-cells showed strong cytotoxicity to three lung cancer cell lines and had significant antitumor effect on squamous lung carcinoma in nude mice. The ex vivo anti-TCRγδ-expanded γδ T-cells prolonged tumor bearing mouse survival and slowed down tumor growth, with similar efficacy to chemotherapy by cis-platinum. Moreover, adoptively transferred human γδ T-cells survived for more than one month in vivo. Finally, γδ T-cells derived from 11 cases of patients with lung cancer had proliferative activity after TCRγδ ligandation, displayed marked cytotoxicity to lung cancer cells and expressed cytotoxicity-or antitumor activity-related molecules, such as perforin, granzyme A and B, Fas ligand, TNFα and IFNγ. Taken together, our finding suggests that anti-TCRγδ expanded γδ T-cells may be used as cellular therapy in treatment of lung cancer.

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Peripheral blood lymphocytes genetically modified to express the self/tumor antigen MAGE-A3 induce antitumor immune responses in cancer patients

Cited by 45 publications

References 31 publications

Immune responses to transgene and retroviral vector in patients treated with ex vivo–engineered T cells

Immune responses to transgene and retroviral vector in patients treated with ex vivo–engineered T cells

Gene Therapy for Skin Diseases

Adoptive immunotherapy of lung cancer with immobilized anti-TCRγδ antibody-expanded human γδ T Cells in peripheral blood

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