Immunogenic Treatment Of Cancer

Abstract

The present invention provides an immunomodulator for use in the treatment and/or control of a neoplastic disease in a patient intended to undergo immunogenic cell death therapy simultaneously, separately or sequentially with administration of the immunomodulator. The therapy can be selected from microwave irradiation, targeted radiotherapy, embolization, cryotherapy, ultrasound, high intensity focused ultrasound, cyberknife, hyperthermia, radiofrequency ablation, cryoablation, electrotome heating, hot water injection, alcohol injection, embolization, radiation exposure, photodynamic therapy, laser beam irradiation, and combinations thereof.

1 - 24 . (canceled) 
     
     
         25 . A immunomodulator composition comprising:
 a non-pathogenic heat-killed whole cell  Mycobacterium  selected from  M. vaccae, M. obuense  and combinations thereof, and   a pharmaceutically acceptable carrier,   
       wherein the composition is for use in treatment and/or control of a neoplastic disease in a patient intended to undergo immunogenic cell death therapy simultaneously, separately or sequentially with administration of the composition. 
     
     
         26 . The immunomodulator composition of  claim 25 , wherein the non-pathogenic heat-killed  Mycobacterium  is a rough variant. 
     
     
         27 . The immunomodulator composition of  claim 25 , wherein the composition is formulated for administration via a parenteral, oral, sublingual, nasal or pulmonary route. 
     
     
         28 . The immunomodulator composition of  claim 27 , which is formulated for parenteral administration via a route selected from subcutaneous, intradermal, subdermal, intraperitonal, intravenous or intravesicular injection. 
     
     
         29 . The immunomodulator composition of  claim 25 , which comprises a unit dose of about 10 6  to about 10 10    Mycobacterium  organisms. 
     
     
         30 . A method of treating, inhibiting or controlling development of a tumour in a subject, the method comprising:
 undertaking immunogenic cell death therapy in the subject; and   administering an effective amount of an immunomodulator composition simultaneously, separately or sequentially with the immunogenic cell death therapy to elicit a protective immune response in the subject, the immunomodulator composition comprising a non-pathogenic heat-killed whole cell  Mycobacterium  selected from  M. vaccae, M. obuense  and combinations thereof.   
     
     
         31 . The method of  claim 30 , wherein said immunogenic cell death therapy is selected from the group consisting of microwave irradiation, targeted radiotherapy, embolisation, cryotherapy, ultrasound, high intensity focused ultrasound, cyberknife, hyperthermia, radiofrequency ablation, cryoablation, electrotome heating, hot water injection, alcohol injection, embolization, radiation exposure, photodynamic therapy, laser beam irradiation, and combinations thereof. 
     
     
         32 . The method of  claim 31 , wherein said immunogenic cell death therapy comprises ionizing radiation. 
     
     
         33 . The method of  claim 30 , wherein the tumour is metastatic. 
     
     
         34 . The method of  claim 30 , wherein the immunomodulator composition is administered via a parenteral route selected from subcutaneous, intradermal, subdermal, intraperitonal, intravenous, or intravesicular injection. 
     
     
         35 . The method of  claim 34 , wherein the parenteral route does not comprise intratumoural injection. 
     
     
         36 . The method of  claim 30 , wherein the immunomodulator composition is administered prior to and/or after the immunogenic cell death therapy. 
     
     
         37 . The method of  claim 36 , wherein administration of the immunomodulator composition occurs in the range of about 4 weeks to about 1 week prior to and/or after the immunogenic cell death therapy. 
     
     
         38 . The method of  claim 37 , wherein administration of the immunomodulator composition comprises administration of one or more aliquots of the composition administered at one or more time intervals in the range of about 4 weeks to about 1 week prior to and/or after the immunogenic cell death therapy and administration to the subject is continued after immunogenic cell death therapy treatment for regression of the tumour. 
     
     
         39 . The method of  claim 30 , wherein the immunomodulator composition is administered to the subject after immunogenic cell death of tumour cells and/or during disease stabilisation. 
     
     
         40 . The method of  claim 30 , wherein said tumour is associated with a cancer selected from prostate cancer, liver cancer, renal cancer, lung cancer, breast cancer, colorectal cancer, breast cancer pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer and soft tissue sarcoma. 
     
     
         41 . The method of  claim 40 , wherein said tumour is associated with colorectal cancer. 
     
     
         42 . The method of  claim 30 , wherein the method comprises an abscopal effect on a neoplastic disease in a patient. 
     
     
         43 . The method of  claim 30 , wherein the effective amount of the immunomodulator composition comprises in the range of about 10 3  to about 10 11    Mycobacterium  organisms. 
     
     
         44 . The method of  claim 30 , wherein the effective amount of the immunomodulator composition comprises in the range of about 0.01 mg to about 1 mg of  Mycobacterium.