Categories of Cancer Immunotherapy

Jane Naberhuis, Ph.D.

The advent and advancement of immunotherapy is rapidly changing the standard of care of many types of cancer. Since approval of the first modern immunotherapy in 19861, dozens of immunotherapies have been approved for clinical use2.

These therapies can be grouped into the following general categories:2,3

  • Monoclonal antibodies. Monoclonal antibodies are produced in a laboratory and designed to identify and attach to specific targets found on cancerous cells. When administered to a patient with cancer, these antibodies highlight malignant cells and enable the immune system to detect and destroy them more efficiently. Over a dozen monoclonal antibodies have been approved by the US Food and Drug Administration (FDA) for the treatment of various types of cancer.
  • Checkpoint inhibitors. These agents do not target tumor cells directly, but instead interfere with the ability of cancer cells to evade immune attack by releasing the "brakes" on the immune system and increasing the ability of T cells to kill malignant cells. The most common targets include programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
  • Adoptive cell transfer. In adoptive cell transfer, T cells are extracted from the tumor microenvironment, and those that are most active against the malignancy are grown in a laboratory before being infused back into the patient. Thus, this treatment aims to enhance the natural cancer-fighting abilities of a patient's own T cells. One particular type of adoptive cell transfer, chimeric antigen receptor (CAR) T cell therapy, utilizes an additional step in which the patients T cells are manipulated through addition of a man-made CAR. This manipulation helps the T cells to more effectively identify specific cancer cell antigens.
  • When it comes to cancer, some vaccines are used in an effort to prevent the disease, and others are used to treat it after it develops. For example, cervical, anal, and throat cancers are associated with human papilloma virus (HPV). Vaccines that guard against HPV infection may prevent the occurrence of these types of cancer. Conversely, the only cancer treatment vaccine currently approved by the FDA is approved for treatment of advanced prostate cancer resistant to hormone therapy.
  • Cytokines are proteins produced by the body that can be largely classified as interferons or interleukins. For instance, interleukin 2 (IL-2) was initially discovered as T cell growth factor, and aids immune cell growth and division. A commercial version of IL-2 has been approved to treat advanced kidney cancer and metastatic melanoma. Of the three types of interferon (alpha, beta, and gamma), only interferon alfa (IFN-alpha) is used to treat cancer. INF-alpha functions by boosting immune activity against cancer cells, and by directly slowing the growth of cancer cells as well as the blood vessels required to support their growth.

Bethyl's cancer portfolio contains over 4,000 antibodies.

Detection of human CD3 (orange), CD8 (cyan), CD68 (green), cytokeratin (yellow), FOXP3 (red) and PD-L1 (magenta) in FFPE tonsil by IHC-IF.
Detection of human CD3 (orange), CD8 (cyan), CD68 (green), cytokeratin (yellow), FOXP3 (red) and PD-L1 (magenta) in FFPE tonsil by IHC-IF. Rabbit anti-CD3E recombinant monoclonal [BL-298-5D12] (A700-016), rabbit anti-CD8 alpha recombinant monoclonal [BLR044F] (A700-044), mouse anti-CD68 monoclonal [KP-1] (A500-018A), mouse anti-cytokeratin monoclonal [AE1/AE3] (A500-019A), rabbit anti-FOXP3 recombinant monoclonal [BLR034F] (A700-034), and rabbit anti-PD-L1 recombinant monoclonal [BLR020E] (A700-020). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P) and HRP-conjugated goat anti-mouse IgG (A90-116P). Substrate: Opal™ 480, 520, 570, 620, 690 and 780. Counterstain: DAPI (blue).
Detection of human PD-1 in FFPE tonsil by IHC.
Detection of human PD-1 in FFPE tonsil by IHC. Antibody: Rabbit anti-PD-1 recombinant monoclonal [BLR076G] (A700-076A). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P). Substrate: DAB.
Detection of human CD3 (cyan), CD8 (green), CD68 (orange), CK (red), Ki67 (yellow) and PD-L1 (white) in FFPE HNSCC by IHC-IF.
Detection of human CD3 (cyan), CD8 (green), CD68 (orange), CK (red), Ki67 (yellow) and PD-L1 (white) in FFPE HNSCC by IHC-IF. Rabbit anti-CD3E recombinant monoclonal [BL-298-5D12] (A700-016), rabbit anti-CD8 alpha recombinant monoclonal [BLR044F] (A700-044), mouse anti-CD68 monoclonal [KP-1] (A500-018A), mouse anti-cytokeratin monoclonal [AE1/AE3] (A500-019A), rabbit anti-Ki-67 monoclonal [BLR021E] (A700-021) and rabbit anti-PD-L1 recombinant monoclonal [BLR020E] (A700-020). Secondary: HRP-conjugated goat anti-rabbit IgG (A120-501P) and HRP-conjugated goat anti-mouse IgG (A90-116P). Substrate: Opal™ 480, 520, 570, 620, 690 and 780. Counterstain: DAPI (blue).

References

1. Talpaz M, Kantarjian HM, McCredie K, et al. 1986. Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia. N Engl J Med. Apr;314(17):1065-9.

2. Tang J, Shalabi A, Hubbard-Lucey VM. 2018. Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol. Jan;29(1):84-91.

3. National Institutes of Health. National Cancer Institute. Immunotherapy to treat Cancer. April 19, 2019.