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HAVCR2 As A Promising Target For Cancer Immunotherapy

HAVCR2 As A Promising Target For Cancer Immunotherapy

Cancer Immunotherapy

Cancer immunotherapy is a type of cancer treatment using the body’s own immune system to fight against cancer. Dr. William Coley is reported to be the first one pioneered the treatment of cancer with immunotherapy. To date, there are mainly three types of cancer immunotherapies: antibody immunotherapy, cellular immunotherapy and cytokine immunotherapy.

This therapy method is based on the fact that cancer cells are generally found containing markers known as tumour-associated antigens (TAAs) on cell surface. The immune system can recognize these cancer cell markers and further attack cancer cells by a serial of immune responses. Immune checkpoints are molecules in the immune system that can either turn up an immune sigal (stimulatory immune checkpoints) or turn down an immune signal (inhibitory immune checkpoints). Many cancers can protect themselves from the immune system attacks. Two well-known inhibitory immune checkpoints, cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 (PD-1), have been proven to be effective targets in fighting cancer. Blockade of these targets promotes the immune system to destroy tumor cells.

Although targeting CTLA4 and PD-1 have achieved revolutionary clinical impact in many cancers, a large portion of cancer patients have not yet benefited from the PD-1 and CTLA-4-based cancer therapy. Therefore, it is much-needed to discover more novel targets for cancer immunotherapy.


Human hepatitis A virus cellular receptor 2 (HAVCR2) is the next promising target for cancer immunotherapy. HAVCR2 is also known as T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), CD366; KIM-3; TIMD3; Tim-3; TIMD-3; HAVcr-2. It is encoded by HAVCR2 gene in human. Accumulating studies support the value of HAVCR2 as a target for cancer immunotherapy.

1) Like CTLA4 and PD-1, HAVCR2 is also one member of inhibitory checkpoint molecules. HAVCR2 protein negatively regulates Th1/Tc1 function by inducing cell death upon interaction with its ligand, galectin-9. In experiments of HAVCR2 blockade, tumor antigen-specific T cells increase proliferation and cytokine production.

2) CTLA4 and PD-1 are known to be over-expressed on all effector T cells. In clinical trails, autoimmune-like toxicities have been observed in patients treated with anti–CTLA-4 or anti–PD-1 antibodies. Ulike CTLA4 and PD-1, HAVCR2 protein is not widely expressed on all T cells but selectively expressed on T cells that have differentiated toward an IFN-g–producing phenotype. The selective expression of HAVCR2 makes it possible to reduce the risk of promoting autoimmune-like side effects. This has been supported by that mice with deficient Havcr2 do not exhibit autoimmunity.

3) The signaling pathway downstream of HAVCR2 is very different from that of CTLA-4 and PD-1. Upon dual blockade of PD-1 and HAVCR2 pathways, T cell function restoration was significantly greater than blockade of single pathway, which suggests coblockade of these two pathways would have remarkable efficacy in the treatment of cancer immunotherapy. The distinctive advantages of targeting HAVCR2 in drug development, together with the improvement of current CTLA4/PD-1 based therapy, scientists are expecting to make a significant breakthrough in the field of cancer immunotherapy.

Our Capability

Creative Biogene provides products and services to assist scientists in studies of HAVCR2 roles in cancer immunotherapy.

Stable cell lines Human HAVCR2 Stable Cell Line-CHO
Human PDCD1 Stable Cell Line-CHO
Mouse Pdcd1 Stable Cell Line-CHO
Human CTLA4 Stable Cell Line-CHO
Mouse CTLA4 Stable Cell Line-CHO
Panoply™ Human LGALS9 Over-expressing Stable Cell Line
Virus particles Human HAVCR2 adenoviral particles
Human HAVCR2 (NM_032782) lentivirus particles
Human PDCD1 adenoviral particles
Human PDCD1 (NM_005018) lentivirus particles
Human CTLA4 lentiviral particles
Human CTLA4 adenoviral particles
Human LGALS9 adenoviral particles
Human LGALS9 (NM_002308) lentivirus particles
Human LGALS9 (NM_009587) lentivirus particles
cDNAs Human HAVCR2 ORF clone (NM_032782.3)
Mouse Havcr2 ORF clone (NM_134250.2)
Mouse Pdcd1 ORF clone(NM_008798.2)
Mouse CTLA4 ORF clone(NM_009843.3)
Human LGALS9 ORF clone(NM_002308.3)
Mouse LGALS9 ORF clone(NM_013584.2)


  1. Coyle AJ, Gutierrez-Ramos JC. The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T cell function. Nature Immunology. 2001; 2: 203-209.
  2. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006; 439: 682-687.
  3. Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002;415:536–41.
  4. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013;369:134–44.
  5. Jin HT, Anderson AC, Tan WG, West EE, Ha SJ, Araki K, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010; 107: 14733-14738.

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