Passive immunotherapeutic strategies for the treatment of malignant gliomas

Abstract

This review provides historical and recent perspectives related to passive immunotherapy for high-grade gliomas. The authors discuss approaches that use lymphokine-activated killer cells, cytotoxic T lymphocytes, and monoclonal antibodies.

Fig. 1

A protocol for AIT using tumor-infiltrating lymphocytes in a patient with melanoma. A similar protocol may be used for patients with GBM, with adoptive transfer of CTLs directly into the tumor resection cavity. ACT, adoptive cell transfer; ELISA, enzyme-linked immunosorbent assay; IFN, interferon. (From Gattinoni L, Powell DJ Jr, Rosenberg SA, et al. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 2006;6(5):383–93; This figure was reproduced with the kind permission of the Nature Publishing Group.)

Fig. 2

Various mechanisms of (A) immune system evasion: (1) HLA down-regulation, (2) costimulation suppression, (3) homing signal suppression, (4) activation of Treg and Th2 subsets, (5) production of immunosuppressive cytokines, and (6) upregulation of inhibitory ligands; and (B) genetic modulations to counter the glioma microenvironment: (1) transgenic TCRs or CARs, (2) intrinsic costimulatory signals, (3) upregulation of homing signals, (4) production of transgenic cytokines, (5) dominant-negative receptors, and (6) depression of negative inhibition. CARs, chimeric antigen receptors; TCR, T-cell receptors; Th2, T helper type 2; Treg, T regulatory. (From Ngo MC, Rooney CM, Howard JM, et al. Ex vivo gene transfer for improved adoptive immunotherapy of cancer. Hum Mol Genet 2011;20(R1):R93–9. This figure was reproduced with the kind permission of Oxford University Press.)

Fig. 3

Mechanisms of action for unlabeled monoclonal antibodies used in passive immunotherapy for the treatment of GBM. Antigen binding can induce subsequent C1 complement binding, activate antibody-dependent cellular cytotoxicity, or alter signaling pathways leading to reduced tumor growth or apoptosis. ADCC, antibody-dependent cellular cytotoxicity. (From Cragg MS, French RR, Glennie MJ. Signaling antibodies in cancer therapy. Cur Opin Immunol 1999;11(5):541–7; This figure was reproduced with the kind permission of Elsevier.)

Fig. 4

(A) T1-weighted and (B) T2-weighted axial postcontrast magnetic resonance imaging of a patient with GBM at baseline and day 23 posttreatment with cetuximab. (From Neyns B, Sadones J, Joosens E, et al. Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 2009;20(9):1596–603. This figure was reproduced with the kind permission of Oxford University Press.)