Cancer is treated via a coordinated treatment regimen that use various compounds and compositions that employ prime-boost vaccination in combination with immune modulatory treatment and biasing of an immune response towards a Th1 profile.

The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

The present disclosure relates to modified human CD122, wherein the modified human CD122 comprises one or more STAT3 binding motifs. In some embodiments, the modified human CD122 is a modified orthogonal human CD122, which can be selectively activated by a cognate orthogonal IL2. The modified human CD122 is able to stimulate robust and sustained STAT3 and STAT5 signaling upon binding to a cognate IL2 ligand.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.

Disclosed herein are methods of cancer treatment comprising administration of a natural killer (NK) cell or cell line in combination with an IL-6 antagonist, such as an antibody to IL-6 or its receptor, especially for treatment of cancer expressing IL-6 receptors and in which checkpoint inhibitory receptors, such as PDL-1 and/or PDL-2 are expressed/upregulated during disease.

The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

Combination therapeutics for the treatment of cancer include the use of immune effector cells, IL-15 based superagonists and one or more immunotherapeutic agents such as Bacillus Calmette-Guerin (BCG).

In the present invention, inventors have used high throughput sequencing to identify novel mutations in ABCA1 in CM ML patient samples. Further studies in a mouse model of myelomonocytic leukemia driven by hematopoietic Tet2 deficiency have shown that these somatic mutations abrogate the tumor suppressor function of WT ABCA1, resulting in the failure to suppress canonical IL3-receptor beta signaling-driven myelopoiesis. The loss of the myelo-suppressive function of ABCA1 mutants can be overcome by raising HDL levels through overexpression of the human apolipoprotein A-1 (apoA-1) transgene. Inventors have also shown that both IL-3Rbeta blocking antibody and cyclodextrin prevented the proliferation of ABCA1 mutant-transduced Tet2 deficient BM cells similar to the effect of ABCA1-WT overexpression. Accordingly, the invention relates to a method for predicting the survival time of a subject NI suffering from CM ML comprising the step identifying at least one ABCA1 and to a method for treating said subject with HDL/ABCA recombinant (ApoA-1); cylodextrin and/or anti-IL-3Rbeta antibody.

The present disclosure provides a replication-competent, recombinant oncolytic vaccinia virus; and compositions comprising the replication-competent, recombinant oncolytic vaccinia virus. The present disclosure also provides use of the vaccinia virus or composition for inducing oncolysis in an individual having a tumor.

The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).