By Kwok Fan Chow

The Kennedy College of Science, Department of Chemistry, invites you to attend a Ph.D. Research Proposal defense by Andrew Zihao Feng entitled “Investigations into the Primary Structural Heterogeneity of a Complex Antigen-Specific MHC-1-IL-2-Fc Fusion Protein.”

Degree: Doctoral
Location: Perry Hall, Room 215
Date: Monday, Dec. 4, 2023
Time: 1:30 p.m.


  • Chair Jin Xu, Department of Chemistry, University of Massachusetts Lowell
  • Matthew Gage, Department of Chemistry, University of Massachusetts Lowell
  • Dongming Xie, Department of Chemistry, University of Massachusetts Lowell
  • Carl Lawton, Department of Chemistry, University of Massachusetts Lowell

ECD-Fc fusion protein therapeutics are highly heterogeneous and require a great deal of effort to fully characterize. While traditional analytical techniques have proven effective at characterizing IgGs, technology and methodology must evolve alongside the development of increasingly complex analytes. Many antibody-based therapeutics, such as bi-specific antibodies and antibody-drug-conjugates, have already arrived at market. Developing robust and consistent characterization methods is critical to maintaining the safety and efficacy of these new drugs. Thus, it is important to identify sources of structural complexity and then utilize existing and readily available technology to characterize those attributes. This allows for developable techniques that can be robustly applied across a variety of different proteins with similar structures and sources of heterogeneity.

C421 is an ECD-Fc fusion protein containing the ECD region of MHC I, a co-factor for stimulating CD8+ T-cell differentiation, an IgG1 Fc region, and an antigen-specific epitope that is separately maleimide-cysteine conjugated following manufacture of the core C421 scaffold. This level of complexity introduces many difficulties when attempting to characterize the final product and assess its stability and structure. Our intention is to progress method development in characterization of C421 to a point where it is possible to consistently characterize the primary structure, PTMs, and conjugation of the antigen-specific epitope of C421. Because the structure of C421 can be so complex, we have divided our analytical strategy into two parallel paths. The first is to enzymatically reduce the PTM heterogeneity in C421 until we are able to characterize the primary structure. The second is to separately characterize and quantify the sources of heterogeneity that we have found in C421. This will hopefully lead us to novel methods that will allow for more complete and constant analysis of highly complex proteins.

All interested students and faculty members are invited to attend.