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 and Irena KOUTNÁ

Basic information

Original name

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

Authors

ŠIMARA, Pavel (203 Czech Republic, guarantor, belonging to the institution), Viktor LUKJANOV (203 Czech Republic, belonging to the institution), Pavel OTÁHAL (203 Czech Republic) and Irena KOUTNÁ (203 Czech Republic, belonging to the institution)

Edition

CAR-TCR Europe Summit, 2020

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30400 3.4 Medical biotechnology

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

RIV identification code

RIV/00216224:14110/20:00118598

Organization unit

Faculty of Medicine

Keywords (in Czech)

CAR T-lymfocyty; solidní nádory; piggyBac transposon

Keywords in English

CAR T-cells; solid tumor; piggyBac transposon

Abstract

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.

Links

NV19-08-00147, research and development project

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

Investor: Ministry of Health of the CR

Citovat

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

Detailed Information on Publication Record