Virus-free production of CAR T-cells for the treatment of solid
tumors

a 2020

Virus-free production of CAR T-cells for the treatment of solid tumors

ŠIMARA, Pavel, Viktor LUKJANOV, Pavel OTÁHAL a Irena KOUTNÁ

Základní údaje

Originální název

Virus-free production of CAR T-cells for the treatment of solid tumors

Autoři

ŠIMARA, Pavel (203 Česká republika, garant, domácí), Viktor LUKJANOV (203 Česká republika, domácí), Pavel OTÁHAL (203 Česká republika) a Irena KOUTNÁ (203 Česká republika, domácí)

Vydání

CAR-TCR Europe Summit, 2020

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30400 3.4 Medical biotechnology

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14110/20:00118598

Organizační jednotka

Lékařská fakulta

Klíčová slova česky

CAR T-lymfocyty; solidní nádory; piggyBac transposon

Klíčová slova anglicky

CAR T-cells; solid tumor; piggyBac transposon

Štítky

rivok

Změněno: 29. 4. 2020 09:47, Mgr. Pavel Šimara, Ph.D.

Anotace

V originále

T-cells with chimeric antigen receptor (CAR) are powerful tool in treatment of oncologic diseases with promising clinical results, mainly in hematologic malignancies. In most of the clinical studies, reliable and efficient lentiviral transduction is used for CAR T-cells generation. However, this method has several drawbacks – e.g. the lentiviral system is expensive and requires special biohazard setting. One of the alternatives is virus-free transposon system. In our lab we investigate transposon piggyBac-based CAR T-cell generation. We focus on antigens GD2 and PSMA which are expressed abundantly on the cancer cells of neuroblastoma or melanoma and prostatic cancer cells respectively. Anti-GD2 and anti-PSMA CAR labeled with MycTag sequence are introduced into T-cells obtained either from buffy coat or peripheral blood of the donors. After 17 days we obtain almost pure population of CAR T-cells in numbers sufficient for an adult patient. Functional testing in vitro revealed that CAR T-cells are specifically activated to interferon-gamma secretion when co-cultured with relevant target cancer cell lines. Specific cytotoxic effect was observed in target cancer cell lines. Our overall aim is to transfer CAR technology into the clinical trial for solid tumor treatment. For this purpose a consortium of three institutions was established in Czech Republic – 1. Masaryk University, Brno (testing of methods in standard laboratory regime), 2. International Clinical Research Center at St. Anne's University Hospital Brno (clean-room facility in the Good Manufacturing Practice (GMP) regime), and 3. Institute of Hematology and Blood Transfusion, Praha (vector production). Close interaction with State Institute for Drug Control is maintained in order to establish the GMP-grade CAR T-cells production supported by proper pharmaceutical documentation.

Návaznosti

NV19-08-00147, projekt VaV

Název: Pre-klinická validace cGMP produkce CAR T-lymfocytů pro léčbu solidních tumorů

Investor: Ministerstvo zdravotnictví ČR, Pre-klinická validace cGMP produkce CAR T-lymfocytů pro léčbu solidních tumorů

Citovat

ŠIMARA, Pavel, Viktor LUKJANOV, Pavel OTÁHAL a Irena KOUTNÁ. Virus-free production of CAR T-cells for the treatment of solid tumors. In CAR-TCR Europe Summit. 2020.

@proceedings{1650682,
   author = {Šimara, Pavel and Lukjanov, Viktor and Otáhal, Pavel and Koutná, Irena},
   booktitle = {CAR-TCR Europe Summit},
   keywords = {CAR T-cells; solid tumor; piggyBac transposon},
   language = {eng},
   title = {Virus-free production of CAR T-cells for the treatment of solid tumors},
   url = {https://cartcr-europe.com/},
   year = {2020}
}

TY  - CONF
ID  - 1650682
AU  - Šimara, Pavel - Lukjanov, Viktor - Otáhal, Pavel - Koutná, Irena
PY  - 2020
TI  - Virus-free production of CAR T-cells for the treatment of solid tumors
KW  - CAR T-cells
KW  - solid tumor
KW  - piggyBac transposon
UR  - https://cartcr-europe.com/
L2  - https://cartcr-europe.com/
N2  - T-cells with chimeric antigen receptor (CAR) are powerful tool in treatment of oncologic diseases with promising clinical results, mainly in hematologic malignancies. In most of the clinical studies, reliable and efficient lentiviral transduction is used for CAR T-cells generation. However, this method has several drawbacks – e.g. the lentiviral system is expensive and requires special biohazard setting. One of the alternatives is virus-free transposon system. In our lab we investigate transposon piggyBac-based CAR T-cell generation. We focus on antigens GD2 and PSMA which are expressed abundantly on the cancer cells of neuroblastoma or melanoma and prostatic cancer cells respectively. Anti-GD2 and anti-PSMA CAR labeled with MycTag sequence are introduced into T-cells obtained either from buffy coat or peripheral blood of the donors. After 17 days we obtain almost pure population of CAR T-cells in numbers sufficient for an adult patient. Functional testing in vitro revealed that CAR T-cells are specifically activated to interferon-gamma secretion when co-cultured with relevant target cancer cell lines. Specific cytotoxic effect was observed in target cancer cell lines. Our overall aim is to transfer CAR technology into the clinical trial for solid tumor treatment. For this purpose a consortium of three institutions was established in Czech Republic – 1. Masaryk University, Brno (testing of methods in standard laboratory regime), 2. International Clinical Research Center at St. Anne's University Hospital Brno (clean-room facility in the Good Manufacturing Practice (GMP) regime), and 3. Institute of Hematology and Blood Transfusion, Praha (vector production). Close interaction with State Institute for Drug Control is maintained in order to establish the GMP-grade CAR T-cells production supported by proper pharmaceutical documentation.
ER  -

ŠIMARA, Pavel, Viktor LUKJANOV, Pavel OTÁHAL a Irena KOUTNÁ. Virus-free production of CAR T-cells for the treatment of solid tumors. In \textit{CAR-TCR Europe Summit}. 2020.

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