Immunotherapeutics Section

Arya Biragyn, (Bira Arya), Ph.D.
Senior Investigator, Chief
Phone: 410-558-8680
Fax: 410-558-8284
E mail: biragyna@mail.nih.gov

Research Focus:  The focus of Dr. Biragyn’s research is to understand the “immunological paradox of aging”; that is, why cancer incidence is enhanced but cancers often grow more slowly in older people, and why autoimmunity is more prevalent in the elderly but older people have poor vaccine responses. He hypothesizes that this may be a reflection of age-associated impairment of the regulatory immune cells. He studies cancer-mediated immunoregulation to gain insight on the role of regulatory immune cells and to develop potent immunotherapeutics tailored for elderly.

His group demonstrated that human memory-type CCR4+ Tregs suppress T cells via granzyme/perforin -independent process involving FasL-Fas signaling (Baatar et al. 2007). They also found that Tregs suppress T cells utilizing the β-galactoside binding protein (βGBP) inducing a non-processive TCR signaling on target T cells (Baatar et al. 2009). Dr. Biragyn also demonstrated the importance of Tregs in breast cancer lung metastasis. This process is regulated by the primary tumor that remotely activates lungs to produce chemokines CCL17 and CCL22, thereby enabling recruitment of CCR4+ cancer cells together with CCR4+ Tregs. The role of Tregs is to kill anti-cancer NK cells with the use of βGBP (Olkhanud et al. 2009). They also reported that this process was controlled by cancer-produced TSLP promoting Th2-skewed immune responses needed for the effective cancer escape (Olkhanud et al. 2011b). Recent findings from Dr. Biragyn’s laboratory indicate that metastasis also requires non-metastatic cancer cells. Non-metastatic cancer cells induce the generation of a unique subset of regulatory B cells from normal B cells. These previously unknown cells, designated tumor-evoked Bregs (tBregs), facilitate lung metastasis by converting normal T cells into FoxP3+ Tregs (Olkhanud et al. 2011a).     

To tackle the poor immune response of traditional vaccines in elderly and cancer patients, Dr. Biragyn is concentrating his efforts on the development of simpler chemokine-based vaccines. He demonstrated the importance of proper antigen processing and the unique ability of chemokine-based vaccines to utilize both MHC class I and II processing pathways (Biragyn et al. 2004, Schiavo et al. 2006). His laboratory generated a number of potent vaccines that target various tumor-associated self antigens, such as embryonic onco-fetal antigen, OFA-iLRP  and SPANX-B (Almanzar et al. 2009, Biragyn et al. 2007, Ruffini et al. 2004). Recently he created a novel vaccine for Alzheimer’s disease. The vaccine retains its activity when used at the onset of the disease despite old age-related immunological impairments of 3xTg-AD mice. Importantly, the vaccine significantly prolonged life span of mice with AD (Olkhanud et al. 2012).