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Biological Therapies
Biological Therapies
Brenda K. Shelton
I. History
A. In 1895, Hericourt and Richet were first to document antitumor immune therapy in humans, defining the immune surveillance theory of cancer development.
B. Primary barrier to development of biological therapy as a cancer treatment modality was ability to generate large quantities of immune substances, resolved by development of recombinant DNA technology in the 1970s.
II. Definitions/Overview
A. Immune activity is the essential homeostatic mechanism protecting a person against potential pathogens and foreign tissues.
B. Biological therapy is defined as use of naturally occurring immune substances to affect the body’s immune responses. Includes activities such as:
1. Immune stimulation
2. Immune augmentation
3. Immune suppression
III. Rationale for Use
A. Proposed Physiologic Activity
1. The discovery of individual tumor-surface antigens (tumor-specific antigens) and tumor-associated antigens has supported the belief that most human cancers have antigens capable of eliciting an immune response.
2. Cells may spontaneously transform to malignancy or mutate after exposure to carcinogens.
3. Once malignant transformation has occurred, the immunologic surveillance system recognizes the neoplastic cell as foreign by the presence of antigens on the surface of the tumor cells.
4. Under normal circumstances, the immune surveillance system destroys the malignant cell in the preclinical stage; however, an impaired immune system will permit malignant cells to proliferate to clinical disease.
B. Evidence Supporting Immunosurveillance Theory
1. Higher incidence rates of cancer in children, elderly, people with immunodeficiency diseases, and in organ transplantation patients.
2. Reports of spontaneous tumor regression.
3. It has also been shown that tumors heavily infiltrated by lymphocytes may have a better prognosis than those that do not demonstrate this characteristic (Reiger, 2001).
C. Antitumor biological agents have been developed based on different proposed mechanisms of altering the host-tumor response so tumor cells are immunologically destroyed.
IV. Biology of Therapy
A. Basic Goals of Anticancer Biotherapy
1. To stimulate direct and indirect immunocompetence
2. To create tumor-specific immunity
3. To induce tumor regression when used adjunctively with other cancer treatments
B. Indications for Biological Therapy
1. Known tumor-associated antigen that can be targeted for destruction (eg, her-2-neu receptor in breast cancer patients).
2. Tumors with high lymphocytic infiltration.
3. Limited disease thought to be more responsive to immunologic manipulation.
4. Tumors for which spontaneous remissions have been reported (eg, malignant melanoma, renal cell carcinoma).
5. Existing or anticipated bone marrow suppression is the clear single indication for restorative biological therapy.
6. Prevention of rejection in organ transplant recipients and suppression of autoimmune disease mechanisms are indications for immunosuppressive immune modulators or monoclonals that target the T lymphocytes.
C. Principles to Determine Patient Eligibility
1. Tumor size: Large tumors are thought to depress the immune system, and less likely to demonstrate an antitumor response with biological therapy because of the slow immunologic destruction induced by these agents.
2. Tumor type: Patients who derive the most benefit from biological therapy have disease that has not progressed beyond stage II and who are not severely immunosuppressed.
3. Immunocompetence: Patients able to generate positive skin test reactions demonstrating active immune responses may have better antitumor response rates. Quantitative assessment of immune function is made by peripheral blood counts, immunoglobulin assays, and bone marrow aspiration.
D. Biological Therapy Administration
1. Treatment scheduling: Treatment should be timed carefully with other anticancer therapies, so the immune system can recover from the effects of these other modalities. Certain chemotherapeutic agents demonstrate synergistic antitumor activity with biotherapeutic agents (eg, 5-fluorouracil and levamisole).
2. Dosage
a. Biotherapy is not dosed according to maximal tolerated dose (MTD).
b. Biological therapy may exert its optimal biological effect at a dose much lower than the MTD.
c. Optimal biological dose (OBD)—the dose which, with a minimum of side effects, produces the optimal desired clinical responses.
3. Evaluation of efficacy
a. Traditional measures of antineoplastic therapy measure tumor size as the primary assessment of successful therapy.
b. Biotherapeutic trials must incorporate measures of biological effects on the immune system, and immunologic assays.
c. Stabilization of disease may be a more accurate objective than reduction of tumor because the objective of biological therapy is immune activation.
V. Classification of Biological Agents:
There is no defined classification system of biological agents because many have multiple immunologic antitumor activities. The general categories and their nursing implications are listed in Table 4-1.
A. Antitumor biotherapy uses active and passive mechanisms to enhance the nonspecific and specific host-tumor immune responses through the use of attenuated live bacteria or their products or through immunochemical agents. Antitumor biotherapy is further subdivided into cytokines, vaccines, and monoclonal antibodies.
1. Cytokines are cell-killer substances modeled after normal human lymphocyte secretions that are administered to enhance normal immune defense mechanisms. Human growth factors (eg, erythropoietin, granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, and platelet colony stimulating factor) are termed cytokines in some texts, but they do not have antitumor properties and are, therefore, described as restorative biotherapy here.
a. Interferons—alfa, beta, gamma
b. Interleukins—interleukin-2
c. Other—tumor necrosis factors (still investigational)
2. Antitumor vaccines are antibodies specifically engineered to destroy particular tumor antigens, theoretically making them tumor-specific, long-lived, and nontoxic. A major problem in vaccine therapy is the identification and purification of relevant antigens to be used in preparing vaccines.
a. Vaccines may be made from animal or human models.
b. Types of cancer vaccines determined by the transport mechanism of the vaccine: recombinant bacteria, protein peptides, nucleic acids, recombinant viruses, transduced cells, modified tumor cells (Kinzler & Brown, 2001).
c. Immunoadjuvants involve the use of transports that primarily activate existing host immune activities rather than replace defective gene sequences (eg, bacteria, interleukin-12, granulocyte-macrophage colony stimulating factor). This category includes the single vaccine product currently licensed as an anticancer therapy (bacillus Calmette-Guérin [BCG]).
d. Dendritic cells are potent antigen-presenting cells that are essential for recognition and destruction of tumor cells. Removal and cytokine activation of human dendritic cells followed by reinfusion is thought to produce effects similar to other immunoadjuvant therapies (Kinzler & Brown, 2001).
3. Monoclonal antibodies are antibodies derived from the fusion of an antibody-producing cell, such as a B lymphocyte, and another cell.
