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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pediatric lymphoid leukemia has the highest cure rate of all pediatric malignancies, yet due to its prevalence, still accounts for the majority of childhood cancer deaths and requires long-term highly toxic therapy. The ability to target B-cell ALL with immunoglobulin-like binders, whether anti-CD22 antibody or anti-CD19 CAR-Ts, has impacted treatment options for some patients. The development of new ways to target B-cell antigens continues at rapid pace. T-cell ALL accounts for up to 20% of childhood leukemia but has yet to see a set of high-value immunotherapeutic targets identified. To find new targets for T-ALL immunotherapy, we employed a bioinformatic comparison to broad normal tissue arrays, hematopoietic stem cells (HSC), and mature lymphocytes, then filtered the results for transcripts encoding plasma membrane proteins. T-ALL bears a core T-cell signature and transcripts encoding TCR/CD3 components and canonical markers of T-cell development predominate, especially when comparison was made to normal tissue or HSC. However, when comparison to mature lymphocytes was also undertaken, we identified two antigens that may drive, or be associated with leukemogenesis; TALLA-1 and hedgehog interacting protein. In addition, TCR subfamilies, CD1, activation and adhesion markers, membrane-organizing molecules, and receptors linked to metabolism and inflammation were also identified. Of these, only CD52, CD37, and CD98 are currently being targeted clinically. This work provides a set of targets to be considered for future development of immunotherapies for T-ALL.
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PMID:Bioinformatic description of immunotherapy targets for pediatric T-cell leukemia and the impact of normal gene sets used for comparison. 2495 20

Adult B-acute lymphoblastic leukemia (B-ALL) does not share the favorable prognosis seen in pediatric patients with the same disease. Less than 50% of patients experience long-term survival and for those adults over age 60, long-term survival is only 10%. At time of relapse, 5-year prognosis is a dismal 7%. Novel and less toxic agents are urgently needed. The last few years have seen a surge in immune therapies for B-ALL. These agents may target CD19, CD20, CD22, and less frequently CD52. Expression of these surface markers and the drugs which target them are discussed. Some immune therapies are simple monoclonal antibodies against B lymphocyte markers such as rituximab, ofatumumab, and epratuzumab. Others are in a class of antibody-drug conjugates which link a highly toxic chemotherapy to a monoclonal antibody for targeted delivery, such as inotuzumab and denintuzumab. Finally, novel immune therapies recruit (in the case of bispecific T cell engager [BiTE]) or modify (in the case of chimeric antigen receptor [CAR] T cells) one's own T cells to fight leukemic cells. This article reviews the rationale, clinical data, and toxicity profiles of immune therapies approved or in late stages of development for B-ALL.
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PMID:Monoclonal antibodies and immune therapies for adult precursor B-acute lymphoblastic leukemia. 2692 Nov

T-cell malignancies often result in poor prognosis and outcome for patients. Immunotherapy has recently emerged as a revolutionary treatment against cancer, and the success seen in CD19 CAR clinical trials may extend to T cell diseases. However, a shared antigen pool coupled with the impact of T-cell depletion incurred by targeting T cell disease remain concepts to be clinically explored with caution. Here we report on the ability of T cells transduced with a CD5CAR to specifically and potently lyse malignant T-cell lines and primary tumors in vitro in addition to significantly improving in vivo control and survival of xenograft models of T-ALL. To extensively explore and investigate the biological properties of a CD5 CAR, we evaluated multiple CD5 CAR constructs and constructed 3 murine models to characterize the properties of CD5 down-regulation, the efficacy and specificity produced by different CD5 CAR construct designs, and the impact of incorporating a CD52 safety switch using CAMPATH to modulate the persistency and function of CAR cells. These data support the potential use of CD5CAR T cells in the treatment of T cell malignancies or refractory disease in clinical settings.
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PMID:Characterization of an Anti-CD5 Directed CAR T-Cell against T-Cell Malignancies. 3200 59