Anti-idiotypic Research Articles

Electrostatic Mapping of Rabies Anti-idiotype Antibody Compared to Rabies Virus Glycoprotein

Rabies is a lethal viral animal disease that assaults the central nervous system. Its glycoprotein is a viral protein that is essential for viral pathogenicity. Initially, the rabies vaccine was produced from nerve tissue, but it is no longer recommended since it causes adverse effects and is less effective. The anti-idiotype antibody vaccination is one option that functions as homologous artificial antigens to the glycoprotein of the rabies virus. The CDR is the structure of anti-idiotypic antibodies that play a role in mimicking epitopes. It may resemble or be identical to epitopes seen in rabies virus glycoproteins. The objective of this study is to determine the affinity of the CDR anti-idiotype antibody for the rabies virus glycoprotein epitope by studying the CDR electrostatic value. This electrostatic value was analyzed by bioinformatics approaches using a webPIPSA server. The findings revealed an electrostatic resemblance between the structure of anti-idiotype antibodies and the rabies virus glycoprotein. Further study will be aimed at collecting electrostatic values from each structure to create an anti-rabies vaccine. Keywords: anti-idiotype antibodies, CDR, electrostatic, rabies, glycoprotein, webPIPSA

Chondroitin Sulfate Proteoglycan 4 (CSPG4) as an Emerging Target for Immunotherapy to Treat Melanoma

Immunotherapies, including checkpoint inhibitor antibodies, have precipitated significant improvements in clinical outcomes for melanoma. However, approximately half of patients do not benefit from approved treatments. Additionally, apart from Tebentafusp, which is approved for the treatment of uveal melanoma, there is a lack of immunotherapies directly focused on melanoma cells. This is partly due to few available targets, especially those expressed on the cancer cell surface. Chondroitin sulfate proteoglycan 4 (CSPG4) is a cell surface molecule overexpressed in human melanoma, with restricted distribution and low expression in non-malignant tissues and involved in several cancer-promoting and dissemination pathways. Here, we summarize the current understanding of the expression and functional significance of CSPG4 in health and melanoma, and we outline immunotherapeutic strategies. These include monoclonal antibodies, antibody–drug conjugates (ADCs), chimeric-antigen receptor (CAR) T cells, and other strategies such as anti-idiotypic and mimotope vaccines to raise immune responses against CSPG4-expressing melanomas. Several showed promising functions in preclinical models of melanoma, yet few have reached clinical testing, and none are approved for therapeutic use. Obstacles preventing that progress include limited knowledge of CSPG4 function in human cancer and a lack of in vivo models that adequately represent patient immune responses and human melanoma biology. Despite several challenges, immunotherapy directed to CSPG4-expressing melanoma harbors significant potential to transform the treatment landscape.

Anti-HIV Humoral Response Induced by Different Anti-Idiotype Antibody Formats: An In Silico and In Vivo Approach.

Despite advancements in vaccinology, there is currently no effective anti-HIV vaccine. One strategy under investigation is based on the identification of epitopes recognized by broadly neutralizing antibodies to include in vaccine preparation. Taking into account the benefits of anti-idiotype molecules and the diverse biological attributes of different antibody formats, our aim was to identify the most immunogenic antibody format. This format could serve as a foundational element for the development of an oligo-polyclonal anti-idiotype vaccine against HIV-1. For our investigation, we anchored our study on an established b12 anti-idiotype, referred to as P1, and proposed four distinct formats: two single chains and two minibodies, both in two different orientations. For a deeper characterization of these molecules, we used immunoinformatic tools and tested them on rabbits. Our studies have revealed that a particular minibody conformation, MbVHVL, emerges as the most promising candidate. It demonstrates a significant binding affinity with b12 and elicits a humoral anti-HIV-1 response in rabbits similar to the Fab format. This study marks the first instance where the minibody format has been shown to provoke a humoral response against a pathogen. Furthermore, this format presents biological advantages over the Fab format, including bivalency and being encoded by a monocistronic gene, making it better suited for the development of RNA-based vaccines.

A novel strategy for an anti-idiotype vaccine: nanobody mimicking neutralization epitope of porcine circovirus type 2.

Vaccination is the most effective method to protect humans and animals from diseases. Anti-idiotype vaccines are safer due to their absence of pathogens. However, the commercial production of traditional anti-idiotype vaccines using monoclonal and polyclonal antibodies (mAb and pAb) is complex and has a high failure rate. The present study designed a novel, simple, low-cost strategy for developing anti-idiotype vaccines with nanobody technology. We used porcine circovirus type 2 (PCV2) as a viral model, which can result in serious economic loss in the pig industry. The neutralizing mAb-1E7 (Ab1) against PCV2 capsid protein (PCV2-Cap) was immunized in the camel. And 12 nanobodies against mAb-1E7 were screened. Among them, Nb61 (Ab2) targeted the idiotype epitope of mAb-1E7 and blocked mAb-1E7's binding to PCV2-Cap. Additionally, a high-dose Nb61 vaccination can also protect mice and pigs from PCV2 infection. Epitope mapping showed that mAb-1E7 recognized the 75NINDFL80 of PCV2-Cap and 101NYNDFLG107 of Nb61. Subsequently, the mAb-3G4 (Ab3) against Nb61 was produced and can neutralize PCV2 infection in the PK-15 cells. Structure analysis showed that the amino acids of mAb-1E7 and mAb-3G4 respective binding to PCV2-Cap and Nb61 were also similar on the amino acids sequences and spatial conformation. Collectively, our study first provided a strategy for producing nanobody-based anti-idiotype vaccines and identified that anti-idiotype nanobodies could mimic the antigen on amino acids and structures. Importantly, as more and more neutralization mAbs against different pathogens are prepared, anti-idiotype nanobody vaccines can be easily produced against the disease with our strategy, especially for dangerous pathogens.IMPORTANCEAnti-idiotype vaccines utilize idiotype-anti-idiotype network theory, eliminating the need for external antigens as vaccine candidates. Especially for dangerous pathogens, they were safer because they did not contact the live pathogenic microorganisms. However, developing anti-idiotype vaccines with traditional monoclonal and polyclonal antibodies is complex and has a high failure rate. We present a novel, universal, simple, low-cost strategy for producing anti-idiotype vaccines with nanobody technology. Using a neutralization antibody against PCV2-Cap, a nanobody (Ab2) was successfully produced and could mimic the neutralizing epitope of PCV2-Cap. The nanobody can induce protective immune responses against PCV2 infection in mice and pigs. It highlighted that the anti-idiotype vaccine using nanobody has a very good application in the future, especially for dangerous pathogens.

Progress in vaccines against peste des petits ruminants virus

Peste des petits ruminants (PPR) is a highly contagious and economically important viral disease of both domestic (goats and sheep) and wild small ruminants. Due to the devastating effect of this disease on livestock and livelihoods, the Food and Agriculture Organization of the United Nations (FAO) and the World Organization for Animal Health (WOAH) endorsed the Global Strategy for the Control and Eradication of PPR (PPR GCES) and launched the PPR Global Eradication Programme (PPR GEP) to eradicate PPRV by 2030. In order to achieve this goal, a potent, safe and efficacious live-attenuated PPR vaccine with long-lasting immunity is available for immunoprophylaxis. However, the live-attenuated PPR vaccines are thermolabile and require maintenance of an effective cold chain to deliver to the field. In addition, infected animals cannot be differentiated from vaccinated ones (DIVA). To overcome these limitations, some new generation PPR vaccines have been developed: poxvirus vaccine, positive and negative marker vaccine through reverse genetic approach, chimeric vaccine, anti-idiotypic vaccine, subunit vaccine, virus-like particles vaccine, edible vaccine and combined vaccines. Novel recombinant PPR DIVA vaccines were evaluated in goats for safety and efficacy, and all vaccinated animals were clinically protected against an intranasal PPRV challenge. Furthermore, newly developed ELISAs were capable of differentiating between infected and vaccinated animals. Therefore, these DIVA vaccines and the associated tests can facilitate the serological monitoring process and speed up global PPR eradication through vaccination.

Anti-Idiotypic mRNA Vaccine to Treat Autoimmune Disorders.

The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs.

Mechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune tolerance.

The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. In vitro studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4+CD25high T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4+ Foxp3+ Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4+ Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing "idiotypic network theory" and "Treg cell theory" into an "anti-idiotypic Treg cell theory." Based on this hypothesis, an "active anti-idiotypic therapy" for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.

Immune Response and Outcome of High-Risk Neuroblastoma Patients Immunized with Anti-Idiotypic Antibody Ganglidiomab: Results from Compassionate-Use Treatments.

(1) Background: High-risk neuroblastoma (HR-NB) is associated with a poor prognosis despite a multimodal high-intensity treatment regimen, including immunotherapy with anti-GD2 monoclonal antibodies (mAb). Here, we investigated the effects of an anti-idiotypic vaccine based on the mAb ganglidiomab that structurally mimics GD2. (2) Methods: Patients with HR-NB treated with anti-GD2 mAb dinutuximab beta and who achieved complete remission after frontline or salvage therapy were offered the vaccine (0.5 mg ganglidiomab adsorbed to Alhydrogel®). Side effects (CTCAE v4.03) and immune responses were determined on each visit. We also evaluated the time to relapse or progression until the last follow-up. (3) Results: Seven HR-NB patients (five frontlines, two relapsed) received 6-22 subcutaneous injections every two weeks. Six of the seven patients showed an immune response. The non-responding patient had a haploidentical stem cell transplantation as part of the previous treatment. No fever, pain, neuropathy, or toxicities ≥ grade 3 occurred during or post-treatment. All immunized patients did not experience relapses or progressions of their neuroblastoma. (4) Conclusions: This is the first-in-man use of the ganglidiomab vaccine, which was well-tolerated, and all patients not pre-treated by haploidentical transplantation developed vaccine-specific immune responses. These findings provide an important basis for the design of prospective clinical trials.

Clinical implications of anti-idiotype antibodies in COVID-19.

Idiotype-based therapeutics have failed to deliver their promise, necessitating rethinking of the concept and its potential to develop a viable immunotherapy method. The idiotype based hypothesis is discussed in this paper in order to produce effective anti-idiotype vaccinations. Polyclonal anti-idiotype reagents have been shown to be more successful in animal models, and a better understanding of the immune response in humans supports the idea that polyclonal anti-idiotype vaccines will be more effective than monoclonal-based anti-idiotype vaccines. This innovative approach can be used to produce therapeutic antibodies in a Biotech-standard manner. The idiotype network has been tweaked in the lab to provide protection against a variety of microbiological diseases. Antibodies to image-idiotype antigens, both internal and non-internal, can elicit unique immune responses to antigens. The current outbreak of severe acute respiratory syndrome 2 (SARS-2) has presented a fantastic chance to use idiotype/anti-idiotype antibodies as a protective regimen, which might be used to treat COVID-19 patients. The development of various effective vaccinations has been crucial in the pandemic's management, but their effectiveness has been limited. In certain healthy people, the development of viral variations and vaccinations can be linked to rare off-target or hazardous effects, such as allergic responses, myocarditis and immune-mediated thrombosis and thrombocytopenia. Many of these occurrences are most likely immune-mediated. The current analysis reveals successful idiotype/anti-idiotype antibody uses in a variety of viral illnesses, emphazising their importance in the COVID-19 pandemic.

Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p < 0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

Current use and development of fish vaccines in China

In the past decades, the aquaculture industry made great progress in China, which contributes more than 70% yield of the world's farmed fish. Along with the rapid growth of fish production, increased emergence and outbreak of numbers of diseases pose harm to the aquaculture industry and food safety. From the efficient, safe, environmental and ethical aspects, vaccines is definitely the most appropriate and focused method to control different kinds of fish diseases. In China, researchers have done huge works on the fish vaccines, and so far six domestic aquatic vaccine products along with one imported aquatic vaccine have obtained the national veterinary medicine certificate. More critically, some new vaccines have also entered the field experiment stage and showed broad market prospects. In the present review, authors summarize seven aquatic vaccines, including the live vaccine against grass carp hemorrhagic disease, the inactivated vaccine against Aeromonas hydrophila sepsis in fish, the live vaccine against Edwardsiella tarda in turbot, the anti-idiotypic antibody vaccine against Vibrio alginolyticus, V. parahaemolyticus, and E. tarda in Japanese flounder, the cell-cultured inactivated vaccine against grass carp hemorrhagic disease, the inactivated vaccine against fish infectious spleen and kidney necrosis virus (ISKNV), and the genetically engineered live vaccine against V. anguillarum in turbot. Moreover, different delivery routes of fish vaccines are also compared in this review, along with differential fish immune response after vaccination. All these efforts will ultimately benefit the healthy and sustainable development of aquaculture industry in China.

1266P - Prognostic significance of tumour tissue NeuGcGM3 ganglioside expression and predictive value of circulating tumour cell count monitoring in patients receiving racotumomab immunotherapy

BackgroundRacotumomab is an anti-idiotype vaccine, a mirror image of N-Glycolylneuraminic acid (NeuGcGM3), which mimics this ganglioside and triggers an immune response in various tumors. In this study we investigated the prognostic significance of tissue NeuGcGM3 expression level and prognostic as well as predictive value of circulating tumor cell count monitoring in patients on Racotumomab treatment. MethodsOut of 48 patients characterized, 40 were non-small cell lung cancer (NSCLC), 12 stage III and 28 stage IV. 19 Adenocarcinoma and 21 Squamous Ca. 2 were small cell lung cancer (SCLC) and 6 with other carcinomas. Male/Female ratio was 3.36(37/11) and median age was 63 (31-84). All patients received Racotumomab as switch maintenance after chemotherapy. 7 PD-L1 (+) Pts also received check point inhibitors on progression. Expression of NeuGcGM3 was detected with 14F7 monoclonal antibody IHC staining and graded as 0,1+,2+ or 3+ according to intensity. Circulating tumor cell (CTC) count was monitored using Cell Sorter throughout the treatment course, before starting Racotumomab and every 3 months or on clinical progression. ResultsNeuGcGM3 IHC were performed 25 out of 48 patients whose paraffin blocks were available. 9 Patients had strong (3+), 12 had (2+) and 4 patients had (1+) NeuGcGM3 staining intensity. There was no statistically significant difference in the mean overall survival of the patients according to IHC staining level (1+) mean OS:55.3 months, (2+) mean OS:40.9 months, and (3+) OS:39.0 months. In 14 Patients, circulating tumor cell count was monitored from the blood and correlated well with clinical outcomes in 11 out of 14 patients (%78.5). Significant reduction of the CTC counts was compatible with clinical response whereas increased CTC counts were early messengers for clinical progression. ConclusionsThis study revealed that any grade of NeuGcGM3 positivity in the tumor tissue is adequate to select a patient for Racotumomab treatment regardless of the IHC intensity. We also concluded that CTC monitoring in patients receiving immunotherapy is a good predictive and prognostic tool. Legal entity responsible for the studyNecdet Uskent. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The Promise of Anti-idiotype Revisited.

The promise of idiotype-based therapeutics has been disappointing forcing a new look at the concept and its potential to generate an effective approach for immunotherapy. Here, the idiotype network theory is revisited with regard to the development of efficacious anti-idiotype vaccines. The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition that polyclonal anti-Idiotype vaccines will be more effective compared to monoclonal-based anti-Idiotype vaccines. This novel strategy can be adapted in Biotech-standard production of therapeutic antibodies.

Validating Anti-Idiotypic Binders for Trastuzumab

Validating Anti-Idiotypic Binders for Trastuzumab

Differential effects of two therapeutic cancer vaccines on short- and long-term survival populations among patients with advanced lung cancer

BackgroundProgress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them. MethodsData from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non–small cell lung cancer patients. Data were fitted to Kaplan-Meier, standard Weibull survival, and two-component Weibull mixture models. Bayesian Information Criterion was used for model selection. ResultsVAXIRA did not modify, neither the fraction of patients with long-term survivals (0.18 in the control group v 0.19 with VAXIRA, P = .88), nor the median overall survival of the patients in the short-term survival subpopulation (6.8 v 7.8 months, P = .24). However, this vaccine showed great benefit for the patients belonging to the subpopulation of patients with long-term survival (33.8 v 76.6 months, P <.0001). CIMAVAX showed impact in the overall survival of both short- and long-term populations (6.8 v 8.8 months, P = .005 and 33.8 v 61.8 months, P = .007). It also increased the proportion of patients with long-term survival (from 0.18 to 0.28, P = .02). ConclusionsThis study shows that therapeutic vaccines produce differential effects on short- and long-term survival populations and illustrates the application of advanced statistical methods to deal with the long-term evolution of patients with advanced lung cancer in the era of immunotherapy.

P1.07-003 Cytolitic Tests with Hyperimmune Patient Sera Is a Good Prognostic Tool in Racotumomab Immunotherapy in Advanced Non-Small Cell Lung Cancer

The preferential accumulation of NeuGcGm3 in a variety of malignant tumors, compared with healthy tissues, made this molecule as an attractive target for cancer immunotherapy. 14F7 monoclonal antibody is a highly specific IgG1 against NeuGcGM3 gangliosid. The immunohistochemical detection of NeuGcGM3 allows the potential selection of patients for specific therapy with anti-idiotype racotumomab cancer vaccine. Racotumomab is an anti-idiotype vaccine, mimics this ganglioside and triggers an immune response.

Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

&lt;p&gt;Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc). This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid) which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.&lt;/p&gt;&lt;p&gt;In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC) who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3&lt;sup&gt;rd&lt;/sup&gt;, 6&lt;sup&gt;th&lt;/sup&gt;, 9&lt;sup&gt;th&lt;/sup&gt;, and 12&lt;sup&gt;th&lt;/sup&gt; months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.&lt;/p&gt;

1093P - Switch maintenance therapy with racotumomab or nimotuzumab vs docetaxel for NSCLC patients

Maintenance therapy is a common strategy in NSCLC treatment that improves PFS and OS. Racotumomab-alum is an anti-idiotypic vaccine that induces immunological response against N-glycolilated gangliosides in NSCLC patients. Nimotuzumab is a humanized anti-EGFR monoclonal antibody that has shown activity in NSCLC patients. The aim of this study is to evaluate safety and efficacy of racotumomab-alum or nimotuzumab versus docetaxel as second line or switch maintenance therapy for advanced NSCLC. This phase III, multicenter, open label, randomized trial is designed to enroll 743 stage IIIB-IV NSCLC patients, after first line therapy, with PS 0-2, with written informed consent. The primary endpoint is OS. Patients are been randomized (2:2:1) to 3 arms: racotumomab-alum, nimotuzumab or docetaxel, and stratified according to response to first line. Racotumomab-alum treatment consists in 5 bi-weekly intradermal doses and re-immunizations every 4 weeks. Nimotuzumab arm receives 6 weekly infusions followed by bi-weekly doses. Docetaxel is used at 75 mg/m2 for 6 cycles, if there are no evidences of progressive disease after 3 cycles. As switch maintenance therapy, both experimental drugs will be classified as non-inferior (NI) to docetaxel, if 1- year OS rate is 36% (HRC/T = 0.66) [ d0 (0,41), d0= - ln HR(C/T)] using a 15% NI margin. Here we report the final analysis in non-progressor patients (n = 237). 93 patients in each experimental arm and 51 in docetaxel arm with at least 1 year follow up were analyzed (ITT). The median OS and 1-year survival rate were 11.4 months (CI: 7.07-12.46) and 48.3 % with nimotuzumab, 9.67 months (CI: 6.52-12.82) and 45.5 % with racotumomab-alum and 9.76 months (CI: 7.07-12.46) and 33.5 % with docetaxel, respectively. Most frequent treatment-related adverse events were induration, local erythema and pain in injection site with racotumomab-alum; myalgia, nausea and fever with Nimotuzumab, and anemia, nausea and malaise after docetaxel. Racotumomab-alum [CI 90% NI (-∞;0.14)] and Nimotuzumab [CI 90% NI (- ∞; -0.002) are non-inferior to docetaxel as switch maintenance therapy. Both experimental treatments were safely administered at primary level of health assistance.

Seguridad de la vacuna anti-idiotípica 1E10 en pacientes con tumores de diversas localizaciones

Cancer is a leading cause of death in Cuba and the world. Lung cancer is the leading cause of death, breast cancer is the second leading cause of death and colorectal cancer is the third leading cause of death. The 1E10 anti-idiotype vaccine is a new immunotherapeutic agent, registered for lung cancer by the Center for Molecular Immunology (CIM). You want to evaluate the safety of this vaccine in the treatment of various cancer sites. To determine the safety adverse events occurred in six clinical trials (one stage I lung, 3 phase II in breast, colon and lung, 1 phase II-III and program expanded use, both in lung) were evaluated. 656 patients were studied. Demographic variables, the characteristics of the disease and adverse events were measured. The studies were balanced with respect to baseline characteristics. The most common adverse events were local reactions associated with 1E10 anti-idiotype vaccine and systemic reactions of mild or moderate intensity that were not related to the administration of the vaccine under study. The 1E10 anti-idiotype vaccine is safe for the low frequency and intensity of adverse events reported.

Induction of protective and therapeutic anti-cancer immunity by using bispecific anti-idiotype antibody G22-I50 for nasopharyngeal carcinoma

Increasing evidence has suggested that bispecific and multivalent antibodies which have more antigen binding sites will improve their immunogenicity. The bispecific anti-idiotype antibody vaccine G22-I50 was obtained through genetic engineering to enhance the immunogenicity of anti-idiotype antibody vaccines G22 and I50. G22-I50 vaccination could induce anti-tumor immunity in the Balb/c mouse model. The protective and therapeutic efficacy of G22-I50 was also evaluated using the hu-PBL–SCID mouse model injected three times with G22-I50, G22, or I50 mixed with Freund's adjuvant. Results demonstrated that the protective anti-tumor effect of G22-I50 could be relevant with the production of Ab3 antibody and activation of CD8+ cytotoxic T-lymphocytes. In preventive and therapeutic experiments, G22-I50 could reduce tumor size and prolong the survival time of HNE2-bearing mice (p<0.05). Human CD8+ T lymphocytes infiltrated the tumor sites, and high levels of human IFN-γ, TNF-α, and caspase-3 were also detected in the tumors from G22-I50-vaccinated and -treated mice. Therefore, the bispecific anti-idiotype antibody vaccine G22-I50 can induce strong humoral and cell-mediated immune responses. This vaccine can be potentially applied to prevent and treat nasopharyngeal carcinoma.