Use of therapeutic compositions for the treatment of patients with tumors of epithelial origin
The present invention relates to the branches of Biotechnology and Medicine. It describes the use of therapeutic compositions comprising a compound that blocks epidermal growth factor and an antibody that blocks the PD-1/PD-1 ligand signaling pathway in the treatment of tumors of epithelial origin, particularly those that express the native form for human KRAS protein. In patients with cancer of epithelial origin expressing native KRAS treated with said therapeutic compositions, an increase in their survival was observed.
1 . A method of treating a tumor of epithelial origin in a patient, comprising administering to the patient i) a vaccine composition that induces the production of specific antibodies (Ab) against epidermal growth factor (EGF) and ii) a compound that blocks PD1/PD1 ligand (PD-L1) signaling pathway, wherein the patient is selected for treatment by determining the presence of human KRAS protein in a sample of the patient's tumoral cells and the human KRAS protein has an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2.
2 . The method of claim 1 , wherein the vaccine composition that induces the Ab production against the EGF comprises a conjugate between human recombinant EGF and a carrier protein.
3 . The method of claim 2 , wherein the carrier protein is selected from the group consisting of:
cholera toxin B subunit,
tetanus toxoid,
KLH and
P64k of Neisseria meningitidis.
4 . The method of claim 3 , wherein the vaccine composition additionally comprises an adjuvant selected from the group consisting of:
incomplete Freund's adjuvants,
squalene-based adjuvants,
synthetic origin adjuvants,
mineral origin adjuvants,
vegetable origin adjuvants,
animal origin adjuvants,
particulated proteic adjuvants and
liposomes.
5 . The method of claim 1 , wherein the compound that blocks PD1/PD-L1 signaling pathway is selected from the group consisting of:
an anti-PD1 Ab and
an anti-PD-L1 Ab.
6 . The method of claim 5 , wherein the anti-PD1 Ab is selected from the group consisting of: nivolumab, pembrolizumab, cemiplimab, MEDI0608 and pidilizumab.
7 . The method of claim 5 , wherein the anti-PD-L1 Ab is selected from the group consisting of: atezolizumab, durvalumab, avelumab and MDX-1105.
8 . The method of claim 1 , wherein the tumor of epithelial origin is selected from the group consisting of: non-small cell lung cancer, squamous cell head and neck cancer, urothelial carcinoma, colorectal cancer, gastric cancer, esophagus cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial carcinoma, breast cancer and skin cancer.
9 . A method of treating a tumor of epithelial origin in a patient comprising: administering a therapeutic regimen to the patient, wherein the therapeutic regimen comprises i) a compound that blocks epidermal growth factor (EGF) and ii) an antibody (Ab) that blocks PD1/PD-L1 signaling pathway, wherein the patient is selected for treatment by determining the presence of human KRAS protein in a sample of the patient's tumoral cells and the human KRAS protein has an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2.
10 . The method of claim 9 , wherein less than 1% of the tumoral cells express PD-L1.
11 . The method of claim 9 , wherein the tumor of epithelial origin is selected from the group consisting of: non-small cell lung cancer, squamous cell head and neck cancer, urothelial carcinoma, colorectal cancer, gastric cancer, esophagus cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial carcinoma, breast cancer and skin cancer.
12 . The method of claim 1 , wherein the tumor of epithelial origin is non-small cell lung cancer.
13 . The method of claim 9 , wherein the tumor of epithelial origin is non-small cell lung cancer.
14 . The method of claim 1 , the tumor of epithelial origin comprises the human KRAS protein.
15 . The method of claim 9 , wherein the tumor of epithelial origin comprises the human KRAS protein.
16 . A method of treating a tumor of epithelial origin in a patient, comprising:
(a) determining that the tumor of epithelial origin comprises human KRAS protein having an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and
(b) administering to the patient i) a vaccine composition that induces the production of specific antibodies (Ab) against epidermal growth factor (EGF) and ii) a compound that blocks PD1/PD1 ligand (PD-L1) signaling pathway.
17 . The method of claim 16 , wherein the tumor of epithelial origin is selected from the group consisting of: non-small cell lung cancer, squamous cell head and neck cancer, urothelial carcinoma, colorectal cancer, gastric cancer, esophagus cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial carcinoma, breast cancer and skin cancer.
18 . The method of claim 16 , wherein the tumor of epithelial origin is non-small cell lung cancer.
19 . The method of claim 16 , wherein the compound that blocks PD1/PD-L1 signaling pathway is selected from the group consisting of:
an anti-PD1 Ab and
an anti-PD-L1 Ab.
20 . The method of claim 19 , wherein the anti-PD1 Ab is selected from the group consisting of: nivolumab, pembrolizumab, cemiplimab, MEDI0608 and pidilizumab.