CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients.
The results demonstrate the superiority of CARs with dual signal domains and confirm a method of comparing CAR-modified T cells within individual patients, thereby avoiding patient-to-patient variability and accelerating the development of optimal T cell immunotherapies.
Inducible apoptosis as a safety switch for adoptive cell therapy.
- A. Di Stasi, Siok-Keen Tey, M. Brenner
- Medicine, BiologyNew England Journal of Medicine
- 2 November 2011
The inducible T-cell safety switch based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization may increase the safety of cellular therapies and expand their clinical applications.
Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients.
Polyclonal donor-derived T-cell lines specific for EBV proteins can be used safely to prevent EBV-related immunoblastic lymphoma after allogeneic marrow transplantation and may also be effective in the treatment of established disease.
Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma
It is shown in individuals with neuroblastoma that EBV-specific CTLs expressing a chimeric GD2-specific receptor indeed survive longer than T cells activated by the CD3-specific antibody OKT3 and expressing the same chimeric receptor but lacking virus specificity.
Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma.
It is shown that GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival.
Long–term restoration of immunity against Epstein–Barr virus infection by adoptive transfer of gene–modified virus–specific T lymphocytes
These findings support wider use of antigen–specific CTLs in adoptive immunotherapy and restore cellular immune responses against EBV, but also established populations of CTL precursors that could respond to in vivo or ex vivo challenge with the virus for as long as 18 months.
Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma.
This first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine Her2- CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence.
Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation
A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells.
Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients.
T-cell immunotherapy that takes advantage of Epstein-Barr virus (EBV)-stimulated immunity has the potential to fill an important niche in targeted therapy for EBV-related cancers and the manufacturing methodology is robust and can be transferred readily from one institution to another without loss of reproducibility.