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.