For forty years, SCI has supported and recognised the excellence of early career scientists, by aiding their studies in the form of an SCI Scholarship.
Since 1985 more than 80 scholarships have been awarded which have not only given the recipients financial assistance, but have enabled them to broaden their network, and strengthen their skills and knowledge. SCI Scholars receive access to publishing and mentoring opportunities and are given a platform to present their work amongst esteemed scientists and industrialists, raising their profile within the scientific community.
Harry Palmer was awarded an SCI Scholarship in 2025. At the end of their scholarship, SCI Scholars present a report to SCI. Read on to find out what he has done in his first year as an SCI Scholar.
"My recent PhD research has focused upon antibody-dependent cellular cytotoxicity, a key mechanism of action for many therapeutic antibodies. However, on-target off-tumour toxicity emerges when high-affinity antibodies bind to healthy cells expressing low levels of the requisite antigen. Existing methods to address this employ biological engineering strategies to attenuate antibody affinity, requiring resource- and time-intensive variant selection and expression. To address these limitations, I have employed covalent fragments to chemically modify specific residues in the antigen-binding sites of antibodies, thereby tuning their associated antigen binding and tumour selectivity.
"I first established workflow conditions to facilitate screening of covalent fragment libraries against antibodies in 384-well plate. This allowed plate-based analysis of the full-length antibody or reduced antibody by intact protein liquid chromatography mass spectrometry (IP-LC/MS), and covalent modification to be quantified. Subsequently, libraries of novel covalent fragments were chemically synthesised in a 384-well plate format. These covalent fragment libraries were incubated directly with model antibodies, and covalent modification was quantified using intact-protein mass spectrometry. This workflow has enabled the synthesis and biological screening of over 1200 covalent fragments against three model antibodies in this project.
"As a result of this screening, three hit covalent fragments were identified which site-selectively modify trastuzumab, a therapeutically relevant monoclonal antibody. Site-selective modification was confirmed by enzymatic digestion experiments, identifying a single amino acid in the antigen-binding domain as the major site of modification in the antibody. This acted as the first example of a de novo covalent fragment modifying an antibody.
"The affinity-attenuated antibody variants were investigated in antibody-dependent cellular cytotoxicity (ADCC)-reporter cell assays, which quantified the level of immune cell stimulation by the antibodies. Importantly, this demonstrated that the modified trastuzumab variants demonstrated up to a 10-fold increase in selectivity for the cell line highly overexpressing the target antigen over the cell line with low target antigen expression, as compared to unmodified trastuzumab. This has key significance for the mitigation of on-target off-tumour toxicity observed in trastuzumab, and for monoclonal antibodies, and provides a novel strategy for increasing the selectivity of antibodies through chemical, post-translational modification. I am currently in the final stages of preparing a first-author manuscript on this project.
"My first year as an SCI scholar has had a strong impact on my professional development. As an SCI scholar I have attended five chemistry symposia this year, including the 5th Alpine Winter Conference on Synthetic and Medicinal Chemistry in St. Anton, Austria, where I was awarded a best poster prize, further supported by an SCI Messel Travel Grant. Additionally, I have expanded my involvement with the College of Scholars, having joined the SCI Organising Committee earlier this year. I greatly look forward to attending the SCI’s AGM, and presenting my research to date to other members of the College of Scholars."
Harry Palmer, GSK/University of Strathclyde Collaborative Industrial PhD Programme