Interstitial quinacrine activates a distinctive immune response effective for tumor immunotherapy.
BACKGROUND
Interstitial immunotherapy consists of the local injection of immune cells or molecules with cytotoxic properties to destroy neoplastic cells. Intratumor injection of quinacrine induces intense recruitment of activated immune cells that leads to necrosis and elimination of experimental malignant neoplasms; this effect seems to be mediated by immune molecules.


METHODS
We measured the tissue content of activated immune cells and various cytokines at different times during the first 8 days after a single interstitial injection of 150 mg quinacrine in rats.


RESULTS
A large cell infiltrate by macrophages, CD4(+), CD8(+), and natural killer cells was evident a few hours after quinacrine injection. In comparison with controls, tissue contents of 4 cytokines had a marked increase: macrophage chemoattractant protein-1 increased 115-fold; interleukin-6, 9-fold; RANTES (regulated on activation, normal T cell expressed and secreted), 13-fold; and macrophage inflammatory protein-2, 10-fold. Other cytokines, like interleukins 1beta, 2, 4, 10, interferon-gamma, tumor necrosis factor-alpha, complement 3, and C reactive protein did not increase significantly, indicating that the endogenous local response to quinacrine follows a singular pathway of immune activation.


CONCLUSIONS
Interstitial quinacrine is a strong activator of innate immunity and is not mediated by the usual mechanisms of immune recognition. It constitutes an original approach for regional immunotherapy of neoplasms that is not mediated solely by induction of local, cytotoxic chemical necrosis.
Sotelo
Julio
J
Neuroimmunology Unit, National Institute of Neurology and Neurosurgery of Mexico, Mexico City, Mexico.
Guevara
Patricia
P
Pineda
Benjamin
B
Diaz
Claudia
C
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007273:Injections, Intramuscular; D015850:Interleukin-6 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D023421:Models, Animal; D009132:Muscles / Q000276:immunology / Q000473:pathology*; D009336:Necrosis; D009369:Neoplasms / Q000628:therapy; D011796:Quinacrine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D011796:Quinacrine