Antigen Treatment Research Articles

Intralesional Quadrivalent Human Papilloma Virus Vaccine Versus Candida Antigen in the Treatment of Multiple Recalcitrant Non-Genital Warts.

Warts are the most prevalent clinical manifestation of Human Papilloma Virus (HPV) infections, which vary in morphological pattern depending on the site of the body affected. To evaluate the safety and efficacy of intralesional quadrivalent HPV vaccine versus candida antigen in treatment of multiple recalcitrant non-genital warts. A randomized-control clinical trial included 60 cases with multiple recalcitrant warts who were randomly distributed into three groups; Group I included 20 patients who received intralesional candida antigen at a dose of 0.3 mL of 1/1000 solution, Group II included 20 patients who received intralesional quadrivalent HPV vaccine at a dose of 0.3ml and Group III included 20 patients who received intralesional injection 0.3 ml of normal saline 0.9% as a control group). Each agent was injected at the base of the largest wart every three weeks until it was completely cleared, or for a total of four sessions. the highest response rate was detected in the quadrivalent HPV vaccine group (75% complete response) followed by the candida vaccine group (40% complete response and 15% partial response). Also, regarding the distant response rate, the highest response rate was detected in the quadrivalent HPV vaccine group (72.7% complete response and 27.3% partial response) followed by the candida vaccine group (33.3% complete response and 50% partial response). Intralesional immunotherapy appears to be effective and safe in treating multiple recalcitrant non-genital warts, with intralesional quadrivalent HPV vaccine outperforming intralesional candida antigen.

Intralesional injection of tuberculin purified protein derivative (PPD) versus measles, mumps, and rubella (MMR) vaccine in treatment of molluscum contagiosum: a comparative study

Molluscum contagiosum (MC) is a skin and mucous membrane infection caused by the molluscum virus (MCV). To evaluate safety and efficacy of intralesional injection of tuberculin purified protein derivative (PPD) antigen injection versus MMR (mumps, measles, rubella) antigen for the treatment of molluscum contagiosum (MC). A total of thirty clinically confirmed patients of molluscum were recruited for this trial. Patients who were divided into three groups (A, B and C). Each group consisted of (30) patients. Group (A) subjects received intralesional MMR injections, group (B) subjects received intralesional PPD injection and group (C) received intralesional saline injection. The results of the present study revealed complete clearance of the injected lesions in 12 patients (80%), partial response in 3 patients (20%) of group (A). In group (B), complete clearance of the treated warts was observed in 11 patients (73.3%) and partial response in 4 (26.7%) of patients. In group (C), the majority of patients 8 (53.3%) demonstrated no response while 7 (46.7%) patients showed only partial clearance. We established a good safety and efficacy profile for tuberculin PPD and MMR antigens in treatment of molluscum contagiosum.

Intralesional injection of purified protein derivative versus Candida antigen in treatment of genital warts.

The Genital warts are common sexually transmitted diseases caused by definite types of human papillomavirus. There are many strategies for the treatment of genital wart and intralesional immunotherapy is considered to be a safe and effective treatment modality. However, there are lack of studies that comparing the clinical effectiveness of intralesional purified protein derivative (PPD) and Candida antigen (CA) in genital wart treatment. To investigate the effectiveness and safety of PPD and CA in the treatment of genital warts. Eighty patients were enrolled in this study and were randomly divided into 2 groups with 40 patients in each. Each antigen was injected intralesionally at a dose of 0.1ml into the largest wart every 2 weeks until complete improvement or for a maximum of four sessions. Complete clinical response was demonstrated in 65%, 62.5% in PPD and CA groups, respectively. There was no statistically difference between both groups. After the 3-month follow-up period, 72.5%, 85% of patients showed complete clearance in PPD and CA groups respectively. Side effects were mild and insignificant in both groups. Recurrence was observed in only one patient in each group. Immunotherapy by intralesional PPD and CA injection is considered to be effective and well-tolerated modalities in treatment of genital wart with minimal side effects and recurrence rate compared to other modalities.

Comparative study between intralesional injection of MMR, BCG, and candida albicans antigen in treatment of multiple recalcitrant warts.

Cutaneous warts represent a challenging condition to treat. To evaluate the safety and efficacy of intralesional injection of MMR (mumps, measles, and rubella) antigen, BCG (bacillus Calmette-Guerin) vaccine, and candida antigen for the treatment of multiple warts. A total of ninety (90) clinically confirmed adult patients complaining of recalcitrant extragenital warts of various sizes and durations were recruited in this randomized clinical trial. They were divided into three groups (A, B, and C). Each group consisted of (30) patients. Group (A) subjects received intralesional MMR injections. Group (B) subjects received intralesional BCG injection and Group (C) received intralesional candida antigen injection. Full clearance of warts was observed in (73.33%, 70%, and 43.33%) in groups A, B, and C, respectively. Infrequent side effects including pain, erythema, and minimal induration were reported in all groups but did not necessitate termination of treatment. All the three modalities used demonstrated a simple, safe modality with low adverse events, and with no recurrence. To achieve an optimal response with an ideal immunotherapeutic agent and ideal dose, further comparative studies are warranted and on different populations and larger sample sizes.

Comparative Study between Intralesional Injection of Vitamin D3 and Candida Albicans Antigen in Treatment of Plantar Warts

Background: Numerous therapeutic modalities have been used either singly or in combination to treat recalcitrant warts. However, a single treatment that is entirely effective in all patients is not yet explored. This might be attributed to the absence of specific antiviral medications against human papilloma virus (HPV) infection. Objective: The aim of this work was to compare efficacy of intralesional vitamin D3 in treatment of plantar warts in comparison to candida albicans antigen. Patients and methods: This study included a total of 40 patients suffering from plantar warts, attending at Dermatology and Andrology Outpatient Clinic, Dermatology Department, Al-Azhar University Hospitals. The included subjects were randomly divided into two groups; Group A (Candida antigen group) consisted of 20 patients, subjected to intralesional injection of candida albicans antigen and Group B: (Vitamin D3 group) consisted of 20 patients, subjected to intralesional injection of Vitamin D3. Results: Results revealed that there were no statistically significant correlations between age, sex of patients, duration of treated warts and clinical response in both treatment groups. However, a statistically significant correlation existed between the number of treated warts and response in Vitamin D group. Complete response occurred in patients with low number of warts. At the end, our results showed that there was no statistically significant correlation in complete response between candida antigen and vitaminD3. Both treatments show comparable efficacy and safety in treatment of plantar warts. Conclusion: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, excellent safety profile and minimal recurrences.

Comparative Study between Intralesional Injection of Vitamin D3 and Candida Albicans Antigen in Treatment of Plantar Warts

Background: Numerous therapeutic modalities have been used either singly or in combination to treat recalcitrant warts. However, a single treatment that is entirely effective in all patients is not yet explored. This might be attributed to the absence of specific antiviral medications against human papilloma virus (HPV) infection. Objective: The aim of this work was to compare efficacy of intralesional vitamin D3 in treatment of plantar warts in comparison to candida albicans antigen. Patients and methods: This study included a total of 40 patients suffering from plantar warts, attending at Dermatology and Andrology Outpatient Clinic, Dermatology Department, Al-Azhar University Hospitals. The included subjects were randomly divided into two groups; Group A (Candida antigen group) consisted of 20 patients, subjected to intralesional injection of candida albicans antigen and Group B: (Vitamin D3 group) consisted of 20 patients, subjected to intralesional injection of Vitamin D3. Results: Results revealed that there were no statistically significant correlations between age, sex of patients, duration of treated warts and clinical response in both treatment groups. However, a statistically significant correlation existed between the number of treated warts and response in Vitamin D group. Complete response occurred in patients with low number of warts. At the end, our results showed that there was no statistically significant correlation in complete response between candida antigen and vitaminD3. Both treatments show comparable efficacy and safety in treatment of plantar warts. Conclusion: Treatment of multiple warts by intralesional injection of candida antigen or vitamin D3 is safe and effective, with good cure rates, excellent safety profile and minimal recurrences.

The Five Immune Forces Impacting DNA-Based Cancer Immunotherapeutic Strategy.

DNA-based vaccine strategy is increasingly realized as a viable cancer treatment approach. Strategies to enhance immunogenicity utilizing tumor associated antigens have been investigated in several pre-clinical and clinical studies. The promising outcomes of these studies have suggested that DNA-based vaccines induce potent T-cell effector responses and at the same time cause only minimal side-effects to cancer patients. However, the immune evasive tumor microenvironment is still an important hindrance to a long-term vaccine success. Several options are currently under various stages of study to overcome immune inhibitory effect in tumor microenvironment. Some of these approaches include, but are not limited to, identification of neoantigens, mutanome studies, designing fusion plasmids, vaccine adjuvant modifications, and co-treatment with immune-checkpoint inhibitors. In this review, we follow a Porter’s analysis analogy, otherwise commonly used in business models, to analyze various immune-forces that determine the potential success and sustainable positive outcomes following DNA vaccination using non-viral tumor associated antigens in treatment against cancer.

Abstract POSTER-THER-1407: Cytotoxic natural human MAb against ovarian carcinoma

Abstract MAb216 is a human IgM mAb encoded in germline configuration by the immunoglobulin heavy chain VH4-34 gene. This antibody and many others derived from the VH4-34 heavy chain gene bind to long chain poly n-acetyl lactosamine (P-NAL) on the cell surface, referred to as the i/I antigen and found on normal fetal red blood cells and mature B cells. We have shown that VH4-34 IgM mAbs that are strong B cell binders also exhibit cytotoxicity to normal and malignant B cells. The mechanism of cytoxicity employed in the absence of complement involves crosslinking of the carbohydrate ligand leading to membrane disruption and loss of cell integrity accompanied by formation of unusual giant pore-like structures on the cell membranes as demonstrated by scanning electron and confocal microscopy. The IgM isotype also activates complement mediated cytotoxicity. Interestingly mAb cytoxicity is greater in vitro at 4 degrees without complement than at room temperature perhaps due to lack of membrane repair. MAb216 has been studied in a phase I trial of acute B cell leukemia, showing some efficacy and no grade 3 toxicity at the doses tested. Recently we found that mAb216 and several similar VH4-34 encoded IgM mAbs bound to the surface of a subpopulation of serous ovarian carcinoma (EOC) cells from individual tumors, ascites and cell lines. Reactivity was assayed using immunofluorescence of live cells or flow cytometry analysis or both. mAb216 was labeled with biotin or directly labeled with Alexa488. The punctate pattern was similar to that seen on B lymphocytes. Of 33 tumor or ascites samples assayed, mAb216 bound to a cell population on 29 specimens (87%). Reactivity ranged from 5-80% of the tumor cells depending on the individual patient. Endometroid (n=3) and mucinous (n=2) ovarian cancer were negative for staining. Three EOC cell lines, OVCAR3, OVCAR5, and Kuramochi show a percent of cells that expressed the P-NAL antigen. OVCAR4, OVCAR8 and SKOV3 did not bind mAb216. In vitro cytotoxicity experiments with ascites and OVCAR3 cell line showed that mAb alone could kill the percent of cells expressing antigen, and the cytotoxicity effects dramatically increased with human complement. Cell death was detected using the CCK-sk assay or flow cytometry counting with propidium iodide to detect dead cells. Like mAb216 cytotoxicity on B lymphocytes, 4 degree temperature enhanced cytotoxicity of OVCAR3 cells. Further, endo-beta-galactosidase treatment removed mAb216 binding and scanning electron microscopy of OVCAR3 showed the same membrane “pores” seen on B lymphocytes after mAb216 treatment. Fluorescence cell sorting of the bright positive population and negative population after mAb216 staining showed that the negative mAb216 population re-expressed the P-NAL antigen by 72 hours indicating that epitope expression is in someway cell cycle or proliferation related. Human VH4-34 IgM mAbs could therefore be used as a new therapy and a new target antigen in treatment of EOC. Preclinical studies are planned. Citation Format: Yi Chen, Marcia Bieber, Neelima Bhat, Nelson N.H. Teng. Cytotoxic natural human MAb against ovarian carcinoma [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1407.

Abstract 2435: Validation of Cynomolgus monkeys as relevant species for safety assessment of a novel human BiTE antibody platform for cancer therapy

Abstract Nonclinical safety assessment of biopharmaceuticals for human use relies on their cross-reactivity with the respective target in other species, the absence of which precludes testing in commonly used animal models. This is the case for a first-generation of T cell-engaging BiTE antibodies, which solely cross-react with T cells of chimpanzee. BiTE antibodies are designed to transiently connect the CD3 subunit of T cell receptors on T cells with an antigen on target cells. This can very effectively activate T cells, leading to a potent redirected lysis of target cells. Here, we have generated a series of novel human anti-CD3 antibodies that cross-react with non-human primate species, including Cynomolgus monkeys (Macaca fascicularis) and marmoset (Callithrix jacchus). The variable domains of a selected anti-CD3 antibody were used to generate next-generation BiTE antibodies specific for (1) CD33, a target antigen for treatment of acute myelogenous leukemia, (2) melanoma-associated chondroitin sulfate proteoglycan (MCSP), a potential target for treatment of melanoma, and (3) epidermal growth factor receptor 1 (EGFR), a validated target for treatment of colorectal cancer. In vitro, CD33-, MCSP- and EGFR-specific BiTE antibodies showed comparable binding to CD3 on human and macaque T cells, and to CHO cells expressing CD33, MCSP and EGFR of human or macaque origin. In human and macaque cell-based assays, bispecific binding triggered redirected target cell lysis as well as conditional T cell activation, as previously described for first-generation BiTE antibodies. When continuously infused for one week to Cynomolgus monkeys, the CD33-specific BiTE antibody caused depletion of CD33-expressing peripheral blood cells at tolerated doses, and reached a maximum tolerated dose (MTD) at 120 µg/m2/day. The EGFR-specific BiTE antibody reached an MTD at 150 µg/m2/kg. In contrast, the MCSP-specific BiTE antibody was well-tolerated up to a dose of 5,000 µg/m2/day. Our primate data suggest that the tolerability and toxicity of CD33-, MCSP- and EGFR-specific BiTE antibodies were apparently determined by target cell-dependent bispecific binding, and not by monovalent binding to CD3 on macaque T cells. Our data validate the Cynomolgus monkey as a relevant species for assessing the safety and tolerability of next-generation BiTE antibodies that use a more broadly cross-reactive anti-CD3 human single-chain antibody. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2435.

Feeding of antigen reduces antigen-binding activity and blunts the secondary response of actively immunized rats

Enteric administration of soluble or particulate antigens to unprimed animals has been repeatedly demonstrated to blunt or abrogate the cellular and humoral immune response to parenteral immunization. We tested the effect of administering bovine serum albumin by gavage or in the drinking water on the serum antigen-binding activity of rats primed by previous immunization with bovine serum albumin and alum. In some animals, this treatment served initially to boost the systemic humoral response; prolonged treatment led to a reduction in antigen-binding activity at a faster rate than wax observed in sham-fed controls. In all rats treated with enteric antigen, the booster response to a second parenteral immunization was reduced or absent. Example of the use of enteric antigen in treatment of patients are cited. On the basis of our findings in rats and those of other investigators who studied mice, as well as the results obtained in patients, it is suggested that further exploration of the enteric approach to treating actively immunized subjects appears warranted.