CAR T cells challenges

Suppressive TME

Trafficking and infiltration

Antigen heterogeneity

T cell exhaustion

Target selection

Immune interviene

Cellular matrix

Metabolic changes

Anaerobic metabolism

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ROS overproduction

M2 macrophage

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Cancer associated fibroblasts

T regs

Checkpoint inhibitors

BBB

selective transport

Perispinal route

fUS (physical destr)

engineered scFv

transcript factor like activation

SNIP cars

Mono

Dual selection ( Math modelling)

TAA

Microenvironment

neo antigen

normal overexpression

abnormal expression

Immune system

BBB

Lymphatic drainage

APC

APC via MHC expression

Escape

natural heterogeneity

low adhesion low immune surveliance

Naive T cells are absent

APC and T cel interaction

glial lyphatic drainage

Intercellular fluid

CSF

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How activated immune cells transmigrate ?

Receptor downregulation

PD 1 downregulation strategies