Research Areas

• Immunomodulation at the Foeto-Maternal Interface
• Immunotoxins
• Virus Entry Inhibitors

Immunomodulation at the Foeto-Maternal Interface

The research group investigates the role of glycodelin-A (GdA) in maintaining foetal tolerance at the foeto-maternal interface.

The foetus expresses paternal allo-antigens and is therefore regarded as non-self by the maternal immune system. Glycodelin-A, secreted by the endometrium under progesterone regulation, is one of the factors involved in protecting the foetus from immune rejection during pregnancy.

Studies from the laboratory have shown that GdA inhibits the proliferation of immune cells and induces apoptosis in activated T cells, NK cells and monocytes through the CD7 receptor, contributing to an immunologically privileged uterine compartment.

Glycodelin & Allograft Rejection

The immunosuppressive properties of glycodelin were also investigated for their possible application in preventing graft rejection.

Because glycodelin is a primate-specific protein, this hypothesis was investigated using an allograft nude mouse model. Cytotoxic cells generated from human peripheral blood lymphocytes decreased the growth of target transplanted human cells in immunologically compromised nude mice.

Addition of physiological concentrations of GdA rescued the target cells from being killed, suggesting a possible role for glycodelin in the management of graft-versus-host reaction.

Immunotoxins

The group has investigated immunotoxins and the construction of vaccines to neutralize abrin-mediated toxicity.

Immunotoxins are constructed by conjugating a cell-surface receptor-specific antibody to a lethal toxin and are being considered for cancer treatment in combination therapy.

Abrin is a type II ribosome-inactivating protein with high catalytic efficiency. In addition to inhibiting protein synthesis, abrin induces apoptosis, making it a candidate for targeted cancer therapy.

The laboratory conjugated the recombinant toxin A chain of abrin to an antibody raised against the human gonadotropin releasing hormone receptor (GnRHR), which is overexpressed in some cancers.

The resulting immunoconjugate inhibited protein synthesis and induced apoptosis specifically in cells expressing GnRHR, providing proof of concept for cell-targeted killing.

The group has also obtained high-affinity monoclonal antibodies capable of protecting mice against lethal doses of abrin and is working to expand the therapeutic window for their effectiveness.

Virus Entry Inhibitors

In a collaborative project on hepatitis C virus (HCV) therapeutics, the group established several monoclonal antibodies that effectively inhibit virus entry into human hepatocytes.

The group also identified and characterised small-molecule inhibitors from plant sources that may be utilised to prevent HCV infection.

Teaching & Academic Contribution

Selected Publications

1. Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes. Soni C., Karande A. A.
   Human Reproduction, 27: 1005–1015, 2012.
2. Abrin immunotoxin: Targeted cytotoxicity and intracellular trafficking pathway. Gadadhar S., Karande A. A.
   PLoS One, 8: e58304, 2013.
   DOI: 10.1371/journal.pone.0058304
3. Mechanistic insights into the neutralization of cytotoxic abrin by the monoclonal antibody D6F10. Bagaria S., Ponnalagu D., Bisht S., Karande A. A.
   PLoS One, 8: e70273, 2013.
   DOI: 10.1371/journal.pone.0070273
4. Identification of a flavonoid isolated from plum (Prunus domestica) as a potent inhibitor of hepatitis C virus entry. Bose M., Kamra M., Mullick R., Bhattacharya S., Das S., Karande A. A.
   Scientific Reports, 7: 3965, 2017.
   DOI: 10.1038/s41598-017-04358-5
5. Immunomodulatory activity of glycodelin: implications in allograft rejection. Dixit A., Balakrishnan B., Karande A. A.
   Clinical and Experimental Immunology, 192: 213–223, 2017.