Biology subjects

Albertini, M. R.

Publications and source records attributed to Albertini, M. R..

2 recordsLinked to original sources

bioRxiv2025

In vitro detection of canine anti-human antibodies following intratumoral injection of the hu14.18-IL2 immunocytokine in spontaneous canine melanoma

BackgroundCanine and human malignant melanoma are naturally occurring cancers with many similarities, making the dog an important parallel patient population to study both diseases. However, development of canine anti-human antibodies (CAHA) needs to be considered when evaluating humanized biotherapeutics in dogs. ObjectivesCharacterize CAHA in sera from dogs with spontaneous melanoma receiving radiotherapy and intratumoral immunocytokine (IT-IC) with humanized 14.18-IL2. MethodsSerum samples were obtained pre-treatment and at several post-treatment times from 12 dogs with locally advanced or metastatic melanoma treated with radiotherapy to the primary site and regional lymph nodes (when clinically involved) followed by IT-IC of humanized 14.18-IL2. Two CAHA assays were developed. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies against the humanized IgG component of hu14.18-IL2. A flow cytometry assay was developed to determine the ability of CAHA to inhibit binding of a mouse anti-GD2 monoclonal antibody to its target. ResultsPost-treatment sera from 7 of 12 dogs developed CAHA levels over pre-treatment that were identified by ELISA as significant increases at Day 30 and/or Day 60. Day 10, Day 30, and Day 60 post-treatment sera from 10 of 12 dogs significantly inhibited the binding of anti-GD2 monoclonal antibody to its target compared to pre-treatment. Significant binding inhibition was also detected in 2 of 12 dogs after local RT but before IT-IC (Day 1). Normal canine sera did not mediate binding inhibition. ConclusionsThis study advances CAHA detection strategies and reports the kinetics of CAHA following IT-IC in dogs with spontaneous melanoma.

immunology↗

bioRxiv2023

Surrogate selection oversamples expanded T cell clonotypes

Inference from immunological data on cells in the adaptive immune system may benefit from modeling specifications that describe variation in the sizes of various clonal sub-populations. We develop one such specification in order to quantify the effects of surrogate selection assays, which we confirm may lead to an enrichment for amplified, potentially disease-relevant T cell clones. Our specification couples within-clonotype birth-death processes with an exchangeable model across clonotypes. Beyond enrichment questions about the surrogate selection design, our framework enables a study of sampling properties of elementary sample diversity statistics; it also points to new statistics that may usefully measure the burden of somatic genomic alterations associated with clonal expansion. We examine statistical properties of immunological samples governed by the coupled model specification, and we illustrate calculations in surrogate selection studies of melanoma and in single-cell genomic studies of T cell repertoires. FundingThis research was supported in part by the National Science Foundation (grant 2023239-DMS), and by grants from the National Institutes of Health: R01 GM102756, P01 CA022443, P01 CA250972, P50 CA278595, UL1 TR002373, P50 CA269011, and P30 CA014520. This work was also supported by resources at the William S. Middleton Memorial Veterans Hospital, Madison, WI, USA, and the UW Carbone Comprehensive Cancer Center. Additional support was provided by Anns Hope Foundation, Taking on Melanoma, the Tim Eagle Memorial, and the Jay Van Sloan Memorial from the Steve Leuthold Family Foundation, philanthropic support in the USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the views of the Dept. of Veterans Affairs or the United States Government.

immunology↗