Page 178 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

Serbian Association for Cancer Research SDIRSACR

P92

Assessment of the Efficacy of a Biomedical Cell Product Production Technology Using Tumor-Infiltrating
Lymphocytes Derived from Surgical Specimens of Patients with Advanced Melanoma

Alexey Bogdanov, Anton Kornev, Andrey Bogdanov, Vitaliy Egorenkov, Fedor Moiseenko, Vyacheslav Chubenko, Nikita
Volkov, Vladimir Moiseenko

N.P. Napalkov Saint Petersburg Clinical Research and Practical Center of Specialized Types of Medical Care (Oncological), Saint
Petersburg, Russia

Keywords: adoptive cell therapy, melanoma, tumor-infiltrating lymphocytes

Background: Adoptive cell therapy of cancer using tumor-infiltrating lymphocytes (TIL) has demonstrated significant
potential, even against refractory tumors. For instance, in melanoma, the rate of objective responses ranges from 40% to
70%, and approximately 10–15% of patients with refractory melanoma achieve durable complete remission. The aim of this
study was to evaluate the efficacy of our developed domestic laboratory technology for producing a biomedical cell product
based on TIL (a TIL-based biomedical cell product, or BMCP-TIL), intended for treating patients with advanced melanoma.
Material and Methods: Operative tissue samples were obtained from 12 patients. Under conditions conducive to
eliminating tumor cells, at least 10⁵ viable TILs were isolated from each sample. During activation, gamma-irradiated
peripheral blood cells from healthy donors, irradiated with a dose of 50 Gy, were used as feeder cells, followed by
the addition of anti-CD3 antibody (OKT3) and interleukin-2. Rapid amplification of TILs was performed in standard
culture flasks until clinically relevant numbers—equal to or exceeding 10⁹ viable TILs—were achieved. Subsequently,
gamma-interferon (IFNγ) production levels were assessed. Following this, TILs were purified from culture medium
components and transferred into infusion bags containing Ringer's solution to produce the BMCP-TIL. Finally, the
resulting TILs were counted and analyzed for viability and cluster of differentiation (CD) surface marker expression.
Results: A complete cycle of BMCP-TIL production was successfully carried out for operative material from 10 out of 12 patients
with advanced melanoma, with the process typically taking 7–8 weeks. Amplified TILs exhibited IFNγ production activity
ranging from 50 to 250 pg/mL. The number of TILs in the final BMCP-TIL product ranged from (1–23)×10⁹ cells, with viability
exceeding 98%. Phenotypic analysis revealed the following distribution of differentiation clusters: CD3+ – (85–99%), among
which CD8+ – (26–95%) and CD4+ – (1–67%), while regulatory T cells (CD25+FoxP3+) accounted for no more than 0.2%.
Conclusions: The high efficiency of the first Russian laboratory technology for producing BMCP-TIL for treating patients
with advanced melanoma has been demonstrated.

Acknowledgments and funding This work was supported by the Health Committee of Saint Petersburg state
assignment for N.P. Napalkov Saint Petersburg Clinical Research and Practical Center of Specialized Types of Medical
Care (Oncological).

P93

Thyroid-cell derived EVs harbour surface thyrotropin-receptor and intravesicular thyroglobulin offering a
novel approach for detecting thyroid cancer recurrence

Nevena Bobar , Ninoslav Mitić , Maja Kosanović , Sonja Šelemetjev , Tijana Išić Denčić , Miloš Žarković , Vladan
1
1
2,4
1
1
1
Živaljević , Jelena Janković Miljuš 1
3,4
1Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Belgrade, Serbia
2Clinic for Endocrine Surgery, University Clinical Center of Serbia, Belgrade, Serbia
3Clinic for Endocrinology, Diabetes and Diseases of Metabolism, University Clinical Center of Serbia, Belgrade, Serbia
4Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Keywords: Cell line, Extracellular vesicles, Tetraspanin, Thyroid cancer, Thyroglobulin, Thyrotropin receptor

Background: Thyroid cancer (TC) poses diagnostic challenges in differentiating benign from malignant tumors and
detecting recurrence, which occurs in 21–27% of patients. Analysis of serum thyroglobulin (Tg) can detect recurrence
early, but the marker is not applicable in patients harboring Tg antibodies (TgAt) due to TgAb interference in standard Tg

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