Développement d’une méthode d’immuno-imagerie permettant d’évaluer le statut immunitaire des tumeurs

Tumor immunogenicity is an important indicator of treatment response, including radiotherapy (RT) and immunotherapy (IT). Immune checkpoint inhibitors have so far yielded only a 15% response rate in unselected patients with squamous cell carcinoma of the head and neck. Imaging the immune microenvironment of the tumor could help guide the selection of patients who might benefit most from IT. Additionally, identifying patients with poorly immunogenic tumors can guide the investigation of additional therapies, including RT, which can increase tumor immunogenicity and improve IT efficacy. The overall objective of this thesis is to develop an immuno-imaging method through the development and validation of a new radiotracer, 89Zr-4HMSA-anti-CD3. The method will be used to track tumor-infiltrating lymphocytes and thus assess the immunogenicity of the tumor. Our data show that the synthesis steps were efficiently carried out and that the product demonstrated stability at >95% ex vivo and in vivo. Cell assays showed that the radiotracer is well absorbed by T cells, with a percentage reaching of 38.36 ± 3.1 %IA/106 cells after 3 days. Furthermore, the competition test with non-radioactive CD3 confirmed the specific binding of 89Zr4HMSA-anti-CD3 to the CD3 marker on T lymphocytes. Additionally, in vivo studies conducted on mouse models with head and neck cancer or colon cancer showed that the developed radiotracer enabled visualization of CD3+ T lymphocyte infiltration into the tumor as observed in preliminary PET images. This result was confirmed by biodistribution data. Moreover, we noted that RT treatment was able to increase lymphocyte infiltration, especially in head and neck cancer (6.08 ± 0.34 %IA/g in the irradiated group vs. 3.05 ± 0.450 %IA/g in the non-irradiated group). Similarly, the co-injection of non-radioactive antiCD3 with the radiotracer showed that, although there was no blocking effect on tumor uptake, a decrease in the uptake of 89Zr-4HMSA-anti-CD3 in the spleen was observed, suggesting a need to review the amount of blocking CD3 used to reinforce the specificity results.

Name thesis:degree_name

M. Sc.

Level thesis:degree_level

Maîtrise

Discipline thesis:degree_discipline

Sciences des radiations et imagerie biomédicale

Grantor dc:publisher

Université de Sherbrooke

Year dc:date.issued

2024

Author dc:creator

• Saidi, Nour Elhouda

Advisors dc:contributor.advisor

• Oweida, Ayman
• Guérin, Brigitte

• Cancer
• CD3
• Lymphocyte T
• Imagerie TEP
• Immunothérapie
• Radiothérapie
• T lymphocyte
• PET imaging
• Immunotherapy
• Radiotherapy

Language dc:language.iso

fr

Handle dc:identifier.uri

http://hdl.handle.net/11143/21973

OAI identifier oai:identifier

oai:usherbrooke.scholaris.ca:11143/21973