Humoral immune response against tumor antigens after treatment with a cancer antigen specific active immunotherapy and its association with improved clinical outcome
AssigneeDendreon Corporation
InventorsDebraj GuhaThakurta, James Trager, Nadeem Sheikh
Life of this patent
Estimating the term…
Abstract
Compositions and methods are provided herein for predicting therapeutic outcome by measuring patient response to cellular antigen specific active immunotherapy (CASAI) using predetermined biomarkers.
Claims43
A method of determining a cancer patient's therapeutic response to cancer antigen specific active immunotherapy (CASAI) treatment with a target cancer antigen, the method comprising the steps of:
- i. obtaining a baseline antibody level reactive to one or more non-target predetermined biomarker antigens;
- ii. treating the cancer patient with CASAI using the target cancer antigen;
- iii. obtaining a post-treatment antibody level reactive to the one or more non-target predetermined biomarker antigens from a patient blood sample after treating with CASAI;
- and,
- iv. measuring differences between the baseline and post-treatment antibody levels reactive to the one or more non-target predetermined biomarker antigens,
- where an increase in the antibody level reactive to the one or more non-target predetermined biomarker antigens over their baseline level predicts a positive therapeutic response.
A method of determining therapeutic response in prostate cancer patients undergoing sipuleucel-T treatment, the method comprising the steps of:
- i. obtaining a baseline level of antibody reactive to one or more non-target predetermined biomarker antigens, said non-target predetermined biomarker antigens selected from the group consisting of PSA, KLK2, KRAS, ERAS, LGALS8, and LGALS3;
- ii. administering to the cancer patient T cells activated ex vivo using a protein comprising a PAP amino acid sequence;
- iii. obtaining a post-treatment antibody level reactive to the one or more non-target predetermined biomarker antigens from a patient blood sample after treating with the activated T cells;
- and,
- iv. measuring differences between the baseline and post-treatment reactive antibody levels to the one or more non-target predetermined biomarker antigens where an increase in antibody level for the one or more non-target predetermined biomarker antigens over their baseline level predicts a positive therapeutic response.
A method of identifying target antigens for cancer treatment with improved patient survival, the method comprising:
- i. obtaining baseline level of antibody reactive to one or more non-target predetermined biomarker antigens;
- ii. treating a patient suffering from cancer with cancer immunotherapy;
- iii. obtaining a post-treatment level of antibody reactive to the one or more non-target predetermined biomarker antigens from a patient blood sample after treating with the cancer immunotherapy;
- iv. comparing the baseline and post-treatment reactive antibody levels to determine one or more non-target predetermined biomarker antigens in which the reactive antibody level is increased;
- v. correlating the increase in the one or more non-target predetermined biomarker antigen reactive antibody levels to an increase in survival;
- and
- vi. identifying the one or more non-target predetermined biomarker antigens in which the increase in reactive antibody levels are correlated with survival as target antigens for cancer treatment with improved patient survival.
A system for determining a cancer patient's therapeutic response to cancer antigen specific active immunotherapy (CASAI) treatment with a target cancer antigen, the system comprising:
- i. a processor;
- ii. a memory coupled with the processor via an interconnect;
- iii. a communications interface coupled with the interconnect and adapted to:
- a. receive a first set of electronic data signals representing a set of pre-treatment interrelated values, each value indicative of a baseline antibody level reactive to one or more non-target predetermined biomarker antigens before CASAI treatment;
- b. receive a second set of electronic data signals representing a set of post-treatment interrelated values corresponding to the set of pre-treatment values, each of the second set of values indicating an antibody level reactive to the one or more non-target predetermined biomarker antigens from a patient blood sample after treating with CASAI;
- iv. a comparison engine coupled with the processor and configured to compare the set of pre-treatment values with the set of post-treatment values to determine which of the set of post-treatment values have changed from the set of pre-treatment values;
- and
- v. an output module configured to provide output data signals representing which of the set of post-treatment values have changed from the set of pre-treatment values, wherein an increase in the antibody level reactive to the one or more non-target predetermined biomarker antigens over their baseline level predicts a positive therapeutic response.
A method of determining therapeutic response in prostate cancer patients undergoing immunomodulatory treatment, the method comprising the steps of:
- i. obtaining a baseline level of antibody reactive to one or more predetermined biomarker antigens, said predetermined biomarker antigens selected from the group consisting of PSA, KLK2, KRAS, ERAS, LGALS8, and LGALS3;
- ii. administering to the prostate cancer patient an immunomodulatory agent;
- iii. obtaining a post-treatment level of antibody reactive to one or more predetermined biomarker antigens from a patient blood sample after treating with the immunomodulatory agent, said predetermined biomarker antigens selected from the group consisting of PSA, KLK2, KRAS, ERAS, LGALS8, and LGALS3;
- and
- iv. comparing differences between the baseline and post-treatment reactive antibody levels to the one or more predetermined biomarker antigens,
- wherein an increase in antibody level for the predetermined biomarker antigens over their baseline level predicts a positive therapeutic response.
Dependencies are inferred from the claim text.