US 9,810,692 B2
Methods for predicting the sensitivity of a subject to immunotherapy
Dalil Hannani, Villejuif (FR); Laurence Zitvogel, Paris (FR); Caroline Robert, Fontenay-aux-Roses (FR); and Nathalie Chaput-Gras, Paris (FR)
Assigned to INSTITUT GUSTAVE ROUSSY, Villejuif (FR)
Appl. No. 14/438,275
Filed by INSTITUT GUSTAVE ROUSSY, Villejuif (FR)
PCT Filed Oct. 25, 2013, PCT No. PCT/EP2013/072367
§ 371(c)(1), (2) Date Apr. 24, 2015,
PCT Pub. No. WO2014/064240, PCT Pub. Date May 1, 2014.
Claims priority of provisional application 61/718,771, filed on Oct. 26, 2012.
Claims priority of application No. 12306329 (EP), filed on Oct. 26, 2012.
Prior Publication US 2015/0268243 A1, Sep. 24, 2015
Int. Cl. G01N 33/574 (2006.01); A61K 39/395 (2006.01); A61K 39/00 (2006.01)
CPC G01N 33/57488 (2013.01) [A61K 39/39541 (2013.01); G01N 33/5743 (2013.01); G01N 33/57484 (2013.01); A61K 2039/5158 (2013.01); G01N 2333/7155 (2013.01); G01N 2333/904 (2013.01); G01N 2800/52 (2013.01)] 12 Claims
 
1. An in vitro method of assessing the sensitivity of a subject having melanoma to an immunotherapeutic molecule acting on the subject's T cells for treating melanoma, which method comprises a step a) of determining, in a biological sample from said subject selected from a blood, a serum, a plasma sample or a derivative thereof, the respective basal expression levels of soluble CD25 (sCD25) and of lactic acid dehydrogenase (LDH), and, when the sCD25 and LDH expression levels are determined, a step b) of comparing said sCD25 and LDH basal levels of expression to sCD25 and LDH, respectively, thereby assessing whether the subject having a tumor is sensitive or resistant to the immunotherapeutic molecule, wherein the immunotherapeutic molecule is an anti-CTLA-4 antibody and:
when the LDH reference expression level is about 500 IU, the step of assessing whether the subject having melanoma is sensitive or resistant to the immunotherapeutic molecule comprises:
i) identifying the subject as having melanoma that is resistant to the immunotherapeutic molecule based on the sCD25 basal expression level being above the sCD25 reference expression level and/or the LDH basal expression level being above the LDH reference expression level of about 500 IU; or
ii) identifying the subject as having melanoma that is sensitive to the immunotherapeutic molecule based on the sCD25 basal expression level being below the sCD25 reference expression level together with the LDH basal expression level being below the LDH reference expression level of about 500 IU; and
iii) administering therapeutic doses of an anti-CTLA-4 antibody to the subject identified as having a melanoma that is sensitive to the immunotherapeutic molecule, or
iv) administering therapeutic doses of an anti-CTLA-4 antibody in combination with therapeutic doses of a compensatory molecule selected from interleukin-2 (IL-2), interleukin-15 (IL-15), IL-2 superkine, sushi IL-15, radioimmunoconjugate of anti-CD25 and immunotoxin or a combination of the compensatory molecules to the subject identified as having a melanoma that is resistant to the immunotherapeutic molecule.