02711nas a2200361   4500000000100000008004100001260001600042653002700058653001200085653003100097653002100128653003000149653002100179653000900200653002400209653002300233653001800256653002800274653001800302653001400320100001400334700001600348700001400364700001100378700001200389700001200401245013000413856006200543300001100605490000800616520171100624022001402335       2012                            d  c2012 Feb 1510aAdjuvants, Immunologic10aAnimals10aCD8-Positive T-Lymphocytes10aCell Line, Tumor10aCytotoxicity, Immunologic10aInterferon-gamma10aMice10aMice, Inbred BALB C10aMice, Inbred C57BL10aMycobacterium10aNeoplasms, Experimental10aT-Lymphocytes10aTh1 Cells1 aRakshit S1 aPonnusamy M1 aPapanna S1 aSaha B1 aAhmed A1 aNandi D00aImmunotherapeutic efficacy of Mycobacterium indicus pranii in eliciting anti-tumor T cell responses: critical roles of IFNγ.  uhttp://onlinelibrary.wiley.com/doi/10.1002/ijc.26099/epdf  a865-750 v1303 a<p>Mycobacterium indicus pranii (MIP) is approved for use as an adjuvant (Immuvac/Cadi-05) in the treatment of leprosy. In addition, its efficacy is being investigated in clinical trials on patients with tuberculosis and different tumors. To evaluate and delineate the mechanisms by which autoclaved MIP enhances anti-tumor responses, the growth of solid tumors consisting of Sp2/0 (myeloma) and EL4 (thymoma) cells was studied in BALB/c and C57BL/6 mice, respectively. Treatment of mice with a single intra-dermal (i.d.) injection of MIP 3 days after Sp2/0 implantation greatly suppresses tumor growth. MIP treatment of tumor bearing mice lowers Interleukin (IL)6 but increases IL12p70 and IFNγ amounts in sera. Also, increase in CD8(+)  T cell mediated lysis of specific tumor targets and production of high amounts of IL2 and IFNγ by CD4(+)  T cells upon stimulation with specific tumor antigens in MIP treated mice is observed. Furthermore, MIP is also effective in reducing the growth of EL4 tumors; however, this efficacy is reduced in Ifnγ(-/-)  mice. In fact, several MIP mediated anti-tumor responses are greatly abrogated in Ifnγ(-/-)  mice: increase in serum Interleukin (IL)12p70 amounts, induction of IL2 and lysis of EL4 targets by splenocytes upon stimulation with specific tumor antigens. Interestingly, tumor-induced increase in serum IL12p70 and IFNγ and reduction in growth of Sp2/0 and EL4 tumors by MIP are not observed in nonobese diabetic severe combined immunodeficiency mice. Overall, our study clearly demonstrates the importance of a functional immune network, in particular endogenous CD4(+)  and CD8(+)  T cells and IFNγ, in mediating the anti-tumor responses by MIP.</p>  a1097-0215