Current chimeric antigen receptor-T (CAR-T) cell therapies are all autolog
ous, single antigen-targeted, rely on viral vectors and only for hematologi
cal malignancies. On other hand, it is still absence of CAR-T cell products f
or treating solid tumors which are allowed with allogeneic application, mu
ltiple targeting and non-viral strategy. In addition, personal manufacturin
g (~2 month) is too long for patients with aggressive disease. Moreover, t
he variable quality of starting cell materials from cancer patient may incre
ases the risk of fail manufacturing and impacts quality of cell products. Th
e present invention: Allogeneic, mRNA-driven, nanobody (Nb)-based CA
R.BiTE-gamma delta (γδ)T cell therapy have several innovative technologi
es as following:
1. Dual targeting HLA-G and PD-L1 for overcoming immune suppressive
microenvironment (TME) in solid tumors.
2. γδT effector cells provide allogeneic potential and MHC-independent n
atural anti-tumor activity to against antigen-low tumor cells.
3. Electroporation of mRNA as non-viral gene delivery strategy to avoid in
sertional mutations.
4. Novel semi-automated close-system is adapted for cultivation of large s
cale and standardized γδT cell products with reducing costs.
5. Cell prototype is adherent to the allogeneic cell therapy guidance of U.
S. FDA, and may allow patient to be treated as soon as the examination wa
s taken in a one-day.
6. CAR.BiTE-γδT cells able to infiltrate into tumor burden, and the released
BiTE triggers bystander immune cells against tumor cells synergically.
7. CAR.BiTE-γδT cell therapy extends 3-5-fold of median survival rate, and
absence of toxicity to normal tissues.
8. Novel CAR construct is more efficiently to maintain effector activity tha
n conventional designs.
9. Low immunogenicity of Nbs able to prevent the production