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Next Generation Leukemia Immunotherapy: New Hope for Leukemia Treatment

Sep 17, 2014 1:00:58 PM / by Shweta

New mode of cancer cell recognition by the immune system opens up a new gateway for leukemia immunotherapy

As described in one of our previous blogs, all malignant tumors have the capability to translate mutant proteins, which could potentially trigger an anti-tumor T cell response[1]. To date, only proteins have been known to activate anti-tumor T cell responses. Recently, scientists at A*STAR's Singapore Immunology Network (SIgN) discovered that leukemia cells have a unique class of lipids which are recognized by specific T cells[2]. By recognizing the lipids, the immune cells elicit an immune response to destroy the leukemia cells. Most interestingly, like proteins, lipids in cancer cells do not differ between individuals, indicating that this specific T cell recognition to lipids happens in all leukemia patients. This new mode of cancer cell recognition can potentially be harnessed for a leukemia immunotherapy that is effective in all patients.

Immunotherapy Identification of immunogenic self- lipid antigens in leukemia cells provides a new conceptual framework for leukemia immune surveillance and possible immunotherapy. Image Credit: http://commons.wikimedia.org/wiki/File:Blausen_0625_Lymphocyte_T_cell.png?fastcci_from=22404040

Leukemia is a type of cancer that usually begins in the bone marrow and results in a high number of white blood cells proliferation. Different types of treatment are available to treat leukemia, but chemotherapy followed by stem cell transplantation is the most widely accepted method to replace abnormal or destroyed malignant cells. Prof Gennaro De Libero and his team have now identified a novel class of self-lipids, methyl-lysophosphatidic acids (mLPA), which accumulate in leukemia cells. They later found that CD1c+ self-reactive T cells are capable of recognizing mLPA in the leukemia cell. The mLPA-specific T-cells stimulate an immune response that activates the T cells to kill the leukemia cells and in turn limits cancer development. In addition to killing CD1c+ leukemia cell lines and primary blasts in vitro, the CD1c-restricted T cells also displayed therapeutic efficacy in a mouse xenograft model of human leukemia.

The identification of a self-lipid antigen that stimulates autoreactive T cells is a novel discovery. This discovery provides proof-of-concept evidence that T cell response against lipids accumulating in acute leukemia could be exploited for leukemia immunotherapy. This knowledge not only sheds light on future leukemia studies but also complements current leukemia immunotherapy studies that run the risk of failure due to re-growth of residual leukemia cells that survive after stem cell transplants. T-cell immunotherapy may serve as a complementary treatment for more effective and safer therapeutic approaches towards leukemia.

Clearly, T cell infusion has potential therapeutic use against cancer. HemaCare is a leading provider of blood products from both healthy and patient donors. Try out our purified lymphocytes obtained from peripheral, bone marrow and cord for research applications in your lab.

References:

[1.] P. van der Bruggen, V. Stroobant, N. Vigneron, B. Van den Eynde, “Tumor antigens resulting from mutations,” Cancer Immunity (2013), http://cancerimmunity.org/peptide/mutations/.

[2.] Lepore M, de Lalla C, Gundimeda SR et al., A novel self-lipid antigen targets human T cells against CD1c+ leukemias. J Exp Med. (2014) Jun 30;211(7):1363-77.

 

 

Topics: Cancer, leukemia, T lymphocytes, Tumors, Basic Research, Immunotherapy (Immunology)

Shweta

Written by Shweta

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