| Title |
Engineering anti-Lewis-Y hu3S193 antibodies with improved therapeutic ratio for radioimmunotherapy of epithelial cancers
|
|---|---|
| Published in |
EJNMMI Research, March 2016
|
| DOI | 10.1186/s13550-016-0180-0 |
| Pubmed ID | |
| Authors |
Ingrid J. G. Burvenich, Fook-Thean Lee, Graeme J. O’Keefe, Dahna Makris, Diana Cao, Sylvia Gong, Angela Rigopoulos, Laura C. Allan, Martin W. Brechbiel, Zhanqi Liu, Paul A. Ramsland, Andrew M. Scott |
| Abstract |
The aim of the study was to explore Fc mutations of a humanised anti-Lewis-Y antibody (IgG1) hu3S193 as a strategy to improve therapeutic ratios for therapeutic payload delivery. Four hu3S193 variants (I253A, H310A, H435A and I253A/H310A) were generated via site-directed mutagenesis and radiolabelled with diagnostic isotopes iodine-125 or indium-111. Biodistribution studies in Lewis-Y-positive tumour-bearing mice were used to calculate the dose in tumours and organs for therapeutic isotopes (iodine-131, yttrium-90 and lutetium-177). (111)In-labelled I253A and H435A showed similar slow kinetics (t 1/2β, 63.2 and 62.2 h, respectively) and a maximum tumour uptake of 33.11 ± 4.05 and 33.69 ± 3.77 percentage injected dose per gramme (%ID/g), respectively. (111)In-labelled I253A/H310A cleared fastest (t 1/2β, 9.1 h) with the lowest maximum tumour uptake (23.72 ± 0.85 %ID/g). The highest increase in tumour-to-blood area under the curve (AUC) ratio was observed with the metal-labelled mutants ((90)Y and (177)Lu). (177)Lu-CHX-A" DTPA-hu3S193 I253A/H310A (6:1) showed the highest tumour-to-blood AUC ratio compared to wild type (3:1) and other variants and doubling of calculated dose to tumour based on red marrow dose constraints. These results suggest that hu3S193 Fc can be engineered with improved therapeutic ratios for (90)Y- and (177)Lu-based therapy, with the best candidate being hu3S193 I253A/H310A for (177)Lu-based therapy. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 93 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 93 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 25 | 27% |
| Student > Master | 9 | 10% |
| Student > Ph. D. Student | 7 | 8% |
| Researcher | 6 | 6% |
| Professor > Associate Professor | 6 | 6% |
| Other | 17 | 18% |
| Unknown | 23 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 16 | 17% |
| Nursing and Health Professions | 13 | 14% |
| Agricultural and Biological Sciences | 7 | 8% |
| Biochemistry, Genetics and Molecular Biology | 5 | 5% |
| Veterinary Science and Veterinary Medicine | 5 | 5% |
| Other | 24 | 26% |
| Unknown | 23 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2016.
All research outputs
#15,371,100
of 22,867,327 outputs
Outputs from EJNMMI Research
#255
of 557 outputs
Outputs of similar age
#194,968
of 326,753 outputs
Outputs of similar age from EJNMMI Research
#8
of 15 outputs
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