Therapeutic single domain antibody
AssigneeSingh Biotechnology, LLC
InventorSunanda Singh
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Abstract
Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1/2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.
Claims20
A pharmaceutical composition comprising:
- (a) a single-domain antibody consisting of SEQ ID NO:1;
- and
- (b) a pharmaceutically acceptable carrier, wherein the single-domain antibody:
- (i) inhibits KRAS GTPase activity;
- and
- (ii) inhibits phosphorylation of STAT3.
A method of treating a KRAS-mutant cancer in a subject, comprising administering to the subject a therapeutically effective amount of a single-domain antibody consisting of SEQ ID NO:
- 1, wherein the single-domain antibody:
- (a) binds intracellular KRAS and inhibits KRAS GTPase activity;
- and
- (b) binds intracellular STAT3 and inhibits phosphorylation of STAT3.
A method of enhancing anti-tumor immunity in a subject having cancer, comprising administering to the subject a therapeutically effective amount of a single-domain antibody consisting of SEQ ID NO:1, wherein the antibody reduces tumor cell surface PD-L1 expression.
Dependencies are inferred from the claim text.