Title: Summary of Existing Problems in CART Therapy
1Summary of Existing Problems in CART Therapy
2CAR-T Therapy
3CAR-T Therapy
To be sure, the CD19-CART cell therapy technology
should be individualized, but in addition to the
CAR T design itself that will affect the
treatment effect, the timing of application, the
patient's basic condition, the dose of infusion,
etc., will have a significant impact on the
clinical effect. Different car gene vectors
affect CART cell function, and currently used
vectors are gamma retroviruses, lentiviruses, and
car t plasmid. Even if the CAR structure is the
same, the CART cells cultured by different
research centers will be very different. In the
composition of the new generation of CAR, a
co-stimulation region was added, and in
particular, the addition of CD28 or CD137 in the
costimulatory region resulted in the
proliferation of cells in vivo and the anti-tumor
activity was significantly enhanced.
4Related Studies
5- The number of CART cell infusions varies widely,
generally between 105 and 107/kg, ideally with
the least number of cells to obtain the best
effect, but these still need more research to
confirm. How to improve curative effect is the
research direction.
6Related Studies
Xu et al. analyzed the clinical trials in 5
centers and summarized the factors that could
improve the efficacy of CART cells pretreatment
of lymphocyte removal, IL-2 infusion, duration of
CART cells 4 weeks, and peak of peripheral
blood CART cells 0.1 The peak of IFN-? was
200pg/ml however, the number of infused T cells
and the ratio of CD4/CD8 were not significant.
Therefore, based on these factors, we can take
corresponding improvements to improve the
efficacy, including the car t cell structure,
from the first to the fourth generation of the
promotion pretreatment and cytokine application
before infusion gene transduction from
retrovirus to lentiviral vector and so on. The
relationship between adverse reaction intensity
and efficacy is also a problem that needs to be
studied. The time of onset of symptoms and the
severity of CRS depend on the inducing drug, the
degree of immune cell activation, and the tumor
burden.
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8Conclusion
9Conclusion
The use of CART cells to specifically target
CD19-positive B-cell lymphoma and leukemia
patients has achieved significant clinical
results and is expected to be widely used.
Although CART therapy is currently conducted for
a relatively short period of time, there is still
a lack of large-scale samples, and many adverse
reactions and complications need to be gradually
discovered and resolved in clinical trials.
However, in the clinical trials reported for the
treatment of B-cell lymphoma and leukemia, CART
showed a very significant effect, especially for
relapsed and refractory patients, thus providing
a basis for a larger-scale, multi-center clinical
study.
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