Compositions for cancer therapy and methods

Abstract

One aspect of this disclosure is directed to a method for treating a cancer in a subject in need thereof by administering to the subject at least a first compound and a second compound together or separately. The first compound is an effective amount of a checkpoint inhibitor optionally with at least one pharmaceutically acceptable carrier. The second compound is an effective amount of an Anti-Tumor Immune Enhancer (ATIE) optionally with at least one pharmaceutically acceptable carrier. The compounds can be administered together or separately.

We claim: 
     
         1 . A composition for treating cancer comprising: a checkpoint inhibitor and ATIE;
 wherein the ATIE is at least one selected from the group consisting of: rI n •ribo(C 4 U) n ; rI n •ribo(C 5 U) n ; rI n •ribo(C 6 U) n ; rI n •ribo(C 7 U) n ; rI n •ribo(C 8 U) n ; rI n •ribo(C 9 U) n ; rI n •ribo(C 10 U) n ; rI n •ribo(C 11 U) n ; rI n •ribo(C 12 U) n ; rI n •ribo(C 13 U) n ; rI n •ribo(C 14 U) n ; rI n •ribo(C 15 U) n ; rI n •ribo(C 16 U) n ; rI n •ribo(C 17 U) n ; rI n •ribo(C 18 U) n ; rI n •ribo(C 19 U) n ; rI n •ribo(C 20 U) n ; rI n •ribo(C 21 U) n ; rI n •ribo(C 22 U) n ; rI n •ribo(C 23 U) n ; rI n •ribo(C 24 U) n ; rI n •ribo(C 25 U) n ; rI n •ribo(C 26 U) n ; rI n •ribo(C 27 U) n ; rI n •ribo(C 28 U) n ; rI n •ribo(C 29 U) n ; rI n •ribo(C 30 U) n ; rI n •ribo(C 31 U) n ; rI n •ribo(C 32 U) n ; rI n •ribo(C 33 U) n ; rI n •ribo(C 34 U) n ; rI n •ribo(C 35 U) n ; rI n •r(C p•23 , G >p ) n ; rI n •ribo(C 4-29 U) n ; rI n •r(C 11-14 U) n ; rI n •ribo(C 30-35 U) n ; rugged dsRNA; and r(Poly A•Poly U) n .   
     
     
         2 . The composition of  claim 1  wherein the composition is a pharmaceutical composition further comprising at least one pharmaceutically acceptable carrier. 
     
     
         3 . The composition of  claim 1  wherein the composition improves progression free survival or life expectancy of a patient administered the composition. 
     
     
         4 . The composition of  claim 1  wherein the composition provides a synergistic effect in treatment of cancer or in inhibition of proliferation of tumor cells. 
     
     
         5 . The composition of  claim 4  wherein the synergistic effect is selected from the group consisting of: inhibiting tumor growth; inducing tumor cell death; increasing tumor regression; preventing tumor recurrence; preventing tumor growth; preventing tumor spread; delaying tumor recurrence; delaying tumor growth; delaying tumor spread; and promoting tumor elimination. 
     
     
         6 . The composition of  claim 1  wherein the composition provides a synergistic effect in treatment of cancer or in inhibition of the proliferation of tumor cells greater than (1) a composition comprising ATIE alone, (2) a composition comprising checkpoint inhibitor alone, or (3) a sum of (1) and (2). 
     
     
         7 . The composition of  claim 1  wherein the ATIE is rI n •r(C 11-14 U) n . 
     
     
         8 . The composition of  claim 1  wherein the checkpoint inhibitor is selected from the group consisting of: an antibody; a monoclonal antibody; a humanized antibody; a fully human antibody; a fusion protein; a PEGylated antibody; a multimeric antibody; an antibody fragment comprising an epitope binding region; and a combination thereof. 
     
     
         9 . The composition of  claim 1  wherein the checkpoint inhibitor comprises an antibody that binds to one or more selected from the group consisting of 2B4; A2aR; B 7 family ligand; B7 H3; B7 H4; Band T lymphocyte attenuator (BTLA); BMA; CD112; CD137; CD160; CD2; CD20; CD226; CD27; CD276; CD28; CD30; CD33; CD40; CD47; CD52; CD70; CD80; CD86; CGEN 15049; CHK 1; CHK2; cytotoxic T-lymphocyte antigen-4 (CTLA-4); DR3; galectin 9 (GALS); GITR; herpesvirus entry mediator (HVEM); ICOS; IDO1; IDO2; Killer-Cell Immunoglobulin-Like Receptor (KIR); LAIR; LAIR1; LAIR2; LIGHT; lymphocyte activation gene 3 (LAG-3); MARCO; OX-40; PD 1; PD L1; PD L2; PS; SIRP alpha; SLAM; T cell immunoreceptor with Ig and ITIM domains (TIGIT); T cell membrane protein 3 (TIM3); V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA); VTCN1; and a combination thereof. 
     
     
         10 . The composition of  claim 1  wherein the checkpoint inhibitor inhibits or interacts with a ligand of a checkpoint protein selected from the group consisting of: 2B4; A2aR; B-7 family ligand; B7-H3; B7-H4; B and T lymphocyte attenuator (BTLA); BMA; CD112; CD137; CD160; CD2; CD20; CD226; CD27; CD276; CD28; CD30; CD33; CD40; CD47; CD52; CD70; CD80; CD86; CGEN-15049; CHK 1; CHK2; cytotoxic T-lymphocyte antigen-4 (CTLA-4); DR3; galectin 9 (GAL9); GITR; herpesvirus entry mediator (HVEM); HVEM; ICOS; IDO1; IDO2; Killer-Cell Immunoglobulin-Like Receptor (KIR); LAG3; LAIR; LAIR1; LAIR2; LIGHT; lymphocyte activation gene 3 (LAG-3); MARCO; OX-40; PD-1; PD-L1; PD-L2; PS; SIRP alpha; SLAM; T cell immunoreceptor with Ig and ITIM domains (TIGIT); T cell membrane protein 3 (TIM3); V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA); VTCN1; and a combination thereof. 
     
     
         11 . The composition of  claim 1  wherein the checkpoint inhibitor is selected from the group consisting of: alemtuzumab (CAM PATH-1H®); AMP-224 (GlaxoSmithKline/Amplimmune); AMP-514 (Amplimmune/AZ); arelumab (Merck Serono); atezolizumab (TECENTRIQ®); AUNP 12 (Aurigene and Pierre Fabre); avelumab; BMS-936559; BMS-986016 (Bristol-Meyers Squibb); cemiplimab)(LIBTAYO®); CP-870;893 (Genentech); CT-011, durvalumab (IMFINIZI®); Galiximab (Biogen Idec); IMP321 (Immutep S.A.); INCB024360 (Incyte)Indoximod (NewLink Genetics); IPH2101 (Innate Pharma/Bristol-Myers Squibb); ipilimumab (YERVOY®); lambrolizumab, lirilumab (Bristol-Myers Squibb); MDX-1105 (Medarex; Inc/Bristol Myer Squibb); MEDI-4736 (Medimmune/AstraZeneca); MEDI-6469 (MedImmune/AZ); MGA271 (Macrogenics); MIHI; Mogamulizumab (Kyowa Hakko Kirin); MPDL3280A (Roche); nivolumab (Bristol-Myers Squibb); NLG-919 (NewLink Genetics); ofatumumab (ARZERRA®); pembrolizumab (KEYTRUDA®); PF-05082566 (Pfizer); pidilizumab (Curetech); rituximab (RITUXAN®); tremelimumab (formerly ticilimumab; CP-675; 206); urelumab (Bristol-Meyers Squibb); Varlilumab (CelIDex Therapeutics); and a combination thereof.