Specificity Of Immunotherapy Research Articles

A review of biologic anti-cancer medicines

Biologic medicines prepared using living organisms by the process of biotechnology have demonstrated improved bioavailability, specificity and effectiveness in the treatment of various diseases especially cancer. Cancer is caused due to malfunctioning of the immune system, and biologic therapy can repair, stimulate, or enhance the immune response. Biologic antibodies prepared in laboratory can bind to the surface of cancer cells and target them in a specific way. They can also work synergistically with chemotherapy to improve the outcome. Since biologics utilize the immune system, it may be advantageous to use them before the immune system is compromised. In spite of these advantages, high cost of these products may limit their use. The first biologic approved for therapeutic use was biosynthetic “human” insulin made by recombinant DNA technology in 1982. Since then, biologics have had a profound effect on rheumatology, dermatology, gastroenterology, oncology, and other medical disciplines. Conventional treatments like surgery and radiotherapy are effective in case of localized tumors, but may not be effective for disseminated disease or tumors located in non-invasive areas that are difficult or dangerous to reach. Despite the potency of cytotoxic chemotherapy and the specificity of immunotherapy, neither method alone has been sufficient to eradicate the disease. There is evidence that standard chemotherapy may work in synergy with active immunization for more effective antitumor immunity, and there is great potential for the combination of these treatment modalities. This review aims to enumerate the various biologic anti-cancer preparations available in market along with their mechanism of action and intended medical use.

Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment.

Glioblastomas (GBMs) are high‐grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just 12–15 months following standard therapy. A combination of interventions targeting tumor‐specific cell surface regulators along with convergent downstream signaling pathways may enhance treatment efficacy. Against this background, we investigated a novel photoimmunotherapy approach combining the cytotoxicity of photodynamic therapy with the specificity of immunotherapy. An EGFR‐specific affibody (ZEGFR:03115) was conjugated to the phthalocyanine dye, IR700DX, which when excited with near‐infrared light produces a cytotoxic response. ZEGFR:03115–IR700DX EGFR‐specific binding was confirmed by flow cytometry and confocal microscopy. The conjugate showed effective targeting of EGFR positive GBM cells in the brain. The therapeutic potential of the conjugate was assessed both in vitro, in GBM cell lines and spheroids by the CellTiter‐Glo® assay, and in vivo using subcutaneous U87‐MGvIII xenografts. In addition, mice were imaged pre‐ and post‐PIT using the IVIS/Spectrum/CT to monitor treatment response. Binding of the conjugate correlated to the level of EGFR expression in GBM cell lines. The cell proliferation assay revealed a receptor‐dependent response between the tested cell lines. Inhibition of EGFRvIII+ve tumor growth was observed following administration of the immunoconjugate and irradiation. Importantly, this response was not seen in control tumors. In conclusion, the ZEGFR:03115–IR700DX showed specific uptake in vitro and enabled imaging of EGFR expression in the orthotopic brain tumor model. Moreover, the proof‐of‐concept in vivo PIT study demonstrated therapeutic efficacy of the conjugate in subcutaneous glioma xenografts.

IT-34 * PILOT STUDY OF COMBINATION OF ANTITUMOR IMMUNOTHERAPY TARGETED AGAINST CYTOMEGALOVIRUS (CMV) PLUS REGULATORY T-CELL INHIBITION IN PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM)

BACKGROUND: Despite aggressive surgery, high-dose focused radiation, and multimechanistic chemotherapy, malignant gliomas (MG) remain almost universally fatal. The inherent biologic specificity of immunotherapy offers the prospect of targeting neoplastic cells more precisely. Dendritic cells (DCs) are endowed with an extraordinary ability to activate CD4+ and CD8+ T-cells, and DCs loaded with antigens derived from tumor cells (CMV pp65-LAMP mRNA) have the potential to induce potent antitumor immunity. Furthermore, regulatory T-cells (TRegs) which induce a state of reversible immunosuppression in MG and can be functionally inactivated with anti-CD25 antibody (Ab), while dramatically enhance vaccine-induced immune responses. METHODS: Eligible were gross totally resected patients (pts) with newly diagnosed GBM. Pts underwent leukapheresis followed by standard of care radiation/temozolomide (XRT/TMZ) therapy. After completion of XRT/TMZ, up to 12 cycles of TMZ 200 mg/m2/x5d were administered. Around Day 21 of the 1st cycle pts also received: anti-CD25 Ab treatment and vaccine #1. Vaccines #2 and #3 were given biweekly following vaccine#1. On Day 21 of the 2nd TMZ cycle Vaccine #4 was administered. Pts were followed with serial MRIs until disease progression. RESULTS: 7 patients (5 males) were treated. No adverse events attributable to vaccine treatment were observed. Median progression free survival was 23.5 months (95% CI:1.7 to 54.1). Median overall survival was 30.3 months (95% CI:11.8 to 60.8). Overall survival was calculated from the start of vaccine therapy to time of death or last contact if alive. CONCLUSION: Treatment with XRT/TMZ, DC vaccine and anti- CD25 Ab was well tolerated and produced encouraging PFS and OS resulting in now ongoing Phase I study. Due to the lack of adverse events the number of vaccines had been increased to 8 (vs. 4) and anti-CD25 antibody is being given with the first two cycles (vs. with 1st cycle only) of adjuvant TMZ.

About Snake bites in children at the Fez University Hospital (Morocco)

The author stresses the importance of the specificity of immunotherapy and identifies the two appropriate antivenoms for North Africa and the Middle East in general, and Morocco in particular. Due to the very good tolerance of new generation antivenoms, the author recommends systematically administer antivenom as early as possible to avoid unfavorable clinical progression, particularly in children and pregnant women..

Efficacy and specificity of immunotherapy with laboratory animal allergen extracts

The clinical and immunologic response to immunotherapy with laboratory animal allergens was evaluated. There were 23 patients; 11 had received immunotherapy with 12 different extracts (five mouse, six rat, one rabbit), and 12 were matched untreated patients. As a group, nine of 23 had seasonal hay fever. Among the treated patients nine of 11 subjectively improved with immunotherapy. Blocking antibody titers were determined by serum inhibition of allergen-induced histamine release. Treated patients had mean blocking antibody levels of G 30 = 59.3 ± 38.7. In the untreated patients the antibody level was low (G 30 = 4.6 ± 3.6). The difference between the two groups was highly significant (t test p < 0.001). The blocking antibody level correlates with both the final weekly allergen dose and also the cumulative allergen dose received during immunotherapy. When pretreatment sera were available a temporal rise in blocking antibody was demonstrated during immunotherapy. In patients allergic to several laboratory animals and treated with one allergen, the blocking antibody response was predominantly specific to the allergen used in immunotherapy. This indicates a lack of cross-reactivity in the IgG response to the major animal allergens. When immunotherapy was discontinued in four patients there was a dramatic decrease in the blocking titer, and after 24 mo the levels were the same as those of untreated patients.

Is desensitization' for ragweed hay fever immunologically specific?

Cell reactivity (the peak percentage release of histamine) to ragweed antigen E and timothy pollen extract was studied in the leukocytes of children chosen for clinical ragweed sensitivity and treated with that antigen. At the beginning of therapy all children had responded to antigen E with &gt;50% histamine release. At the time studied the cells of about one third released &lt;50% to antigen E and their cell reactivity to timothy pollen (with which they had not been treated) correlated significantly (p &lt;0.001). While there was a significant correlation (p &lt;0.001 ) between the sensitivity (concentration of antigen required for 30% histamine release) and reactivity of the cells to each antigen, there was no correlation between the sensitivity of the cells to the two antigens. It is suggested that immunotherapy to one antigen decreased cell reactivity to both that antigen and to a non-cross-reacting antigen. Since decreased cell reactivity after immunotherapy has been shown by some investigators to be correlated with a positive clinical result, these studies raise a question as to the antigeníc specificity of immunotherapy.