RAISING YOUR LITERATURE CONSCIOUSNESS

D.Campana et.al, Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia (2004) 18, 676-684.

Tumor antigens are often unmutated self-antigens. Immune effector cells bearing receptors specific for those antigens may therefore be deleted or inactivated prior to the emergence of the cancer cell clone.The cells are thus unavailable for priming by a direct tumor vaccination approach. Re-targeting of immune effector cells by providing them with cell surface receptors of the desired tumor antigen specificity may be one form of adoptive immunotherapy particularly relevant to the treatment of cancer. Re-deployment of potent immune effector cells (e.g. cytolytic T lymphocytes (CTL)) having other endogenous specificities, by transduction of the CTL with engineered antigen receptors, could circumvent the self-tolerance barrier and allow efficient CTL elimination of tumor cells.

Dr. Dario Campana and his colleagues have pursued such a strategy for the treatment of B-lineage acute lymphoblastic leukemia (ALL). Virtually all B-lineage ALL tumor cells, in many patients, express the CD19 protein on their cell surface, making CD19 an attractive tumor target antigen for this cancer type. Normal B cells also express CD19, so CD19-specific CTL are deleted or tolerized during their development. In a recent report, Dr. Campana has illustrated the therapeutic potential of CTL re-targeting via transduction of a designer antigen-receptor composed of an antibody-derived anti-CD19 extracellular domain fused to intracellular signaling domains from the CD3 zeta chain and the 4-1BB co-stimulatory molecule. This fusion receptor molecule, when expressed on the transduced CTL, provides the three critical functions required for CTL activation and tumor cell killing: (1) recognition of the tumor antigen, via the anti-CD19 domain; (2) activation of the TcR/CD3 signaling (“Signal 1"), via the CD3 zeta portion; and (3) activation of the co-stimulatory signaling pathway important for CTL proliferation and survival (“Signal 2"), via the 4-1BB portion. Re-targeted CTL were able to efficiently and specifically eliminate CD19-expressing B-ALL tumor cells in in vitro assays, even when the B-ALL tumor cells were in vast excess over the CTL. Bone marrow stromal cells that normally promote the survival of B-ALL tumor cells did not interfere with the cytolosis. These results form the foundation for future in vivo adoptive T cell immunotherapy studies using this CTL re-targeting strategy.

What you need to know

           about the NIH Data Sharing Policy

           about Fellowship Awards

NIH Data Sharing Brochure

The NIH has developed a handy little printable brochure that summarizes elements of the NIH Data Sharing Policy. Data sharing is essential to speed the translation of research results into knowledge, products and procedures to improve human health. All investogator-initiated applications withy direct costs greater than $500,000 in any single year will be expected to discuss their data sharing plan with their program contact at the time they negotiate an agreement with the Institute staff to accept assignment of their application. For more info on the data sharing policy including the final NIH statement on Sharing Research data go to http://grants2.nih.gov/grants/policy/data_sharing.

Fellowship Awards

If you're looking for a way to support a student or a post doctoral fellow in your lab, a fellowship award may provide up to 5 years of support.

F31 or Predoctoral Individual National Research Service Award, provides predoctoral individuals with supervised research training in specified health and health related areas leading towards a research degree (Ph.D.)

F32 or Postdoctoral Individual National Research Service Award is used to provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. You must apply using a specific program announcement.

F33 or National Research Service Awards for Senior Fellows, provide opportunities for experienced scientists to make major changes in the directions of research careers, to broaden scientific background, acquire new research capabilities, acquire experience in an allied research field, or to take time from regular professional responsibilities for the purpose of increasing capabilities to work in health-related research. Applications for the F33 award are thru a Specific program announcement.

For more information and program announcements for F awards, go to the Grant Guidelines.

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