<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>2304-0106</journal-id>
<journal-title><![CDATA[Anales de la Academia de Ciencias de Cuba]]></journal-title>
<abbrev-journal-title><![CDATA[Anales de la ACC]]></abbrev-journal-title>
<issn>2304-0106</issn>
<publisher>
<publisher-name><![CDATA[Academia de Ciencias de Cuba]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S2304-01062022000100031</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Nuevas contribuciones al estudio de los efectores inmunológicos inducidos con la inmunoterapia activa específica CIGB-247]]></article-title>
<article-title xml:lang="en"><![CDATA[Novel contributions to the study of immunological effectors induced by the specific active immunotherapy CIGB-247]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Sánchez Ramírez]]></surname>
<given-names><![CDATA[Javier]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Morera Díaz]]></surname>
<given-names><![CDATA[Yanelys]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Bequet Romero]]></surname>
<given-names><![CDATA[Mónica]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hernández Bernal]]></surname>
<given-names><![CDATA[Francisco]]></given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ayala Ávila]]></surname>
<given-names><![CDATA[Marta]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gavilondo Cowley]]></surname>
<given-names><![CDATA[Jorge V.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Martin Bauta]]></surname>
<given-names><![CDATA[Yenima]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Selman-Housein Bernal]]></surname>
<given-names><![CDATA[Katty-Hind]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[de la Torre Santos]]></surname>
<given-names><![CDATA[Ana Victoria]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Pérez de la Iglesia]]></surname>
<given-names><![CDATA[Mariela]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Trimiño Lorenzo]]></surname>
<given-names><![CDATA[Lian]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Limonta Fernández]]></surname>
<given-names><![CDATA[Miladys]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Centro de Ingeniería Genética y Biotecnología  ]]></institution>
<addr-line><![CDATA[ La Habana]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Centro de Investigaciones Médico Quirúrgicas  ]]></institution>
<addr-line><![CDATA[ La Habana]]></addr-line>
<country>Cuba</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Hospital Celestino Hernández  ]]></institution>
<addr-line><![CDATA[ Santa Clara]]></addr-line>
<country>Cuba</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>04</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>04</month>
<year>2022</year>
</pub-date>
<volume>12</volume>
<numero>1</numero>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_arttext&amp;pid=S2304-01062022000100031&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_abstract&amp;pid=S2304-01062022000100031&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://scielo.sld.cu/scielo.php?script=sci_pdf&amp;pid=S2304-01062022000100031&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN  Objetivos:  Esta investigación tiene como objetivo estudiar los efectores inmunológicos que se inducen en los pacientes inmunizados con el CIGB-247, que incluyen elementos humorales y celulares. Este estudio pretende detectar las diferentes clases y subclases de inmunoglobulinas, evaluar su especificidad por epítopes relevantes en el VEGF y demostrar la presencia de linfocitos CD8+ citotóxicos específicos. También, este trabajo se propone presentar las primeras evidencias preliminares de la posibilidad de combinar el CIGB-247 con otros regímenes oncoterapéuticos.  Métodos:  Para el estudio de los efectores inmunológicos, se realizó el seguimiento inmunológico por las técnicas de ELISA y ELISPOT a los pacientes de los estudios CENTAURO, CENTAURO-2 y Programa de Uso Compasional.  Resultados:  Se demostró que la inmunización induce anticuerpos de clase IgM e IgA específicas al VEGF. En algunos pacientes de larga supervivencia, se produjo una maduración de la respuesta de anticuerpos, representado por el cambio desde IgG1 hacia la subclase IgG4 de mayor afinidad. Se demostró que la repuesta de anticuerpos bloquea la interacción entre el VEGF y los receptores VEGFR2 y VEGFR1. Esta respuesta policlonal específica al VEGF está dirigida a un epítope relevante para su actividad pro-angiogénica, al inhibir su interacción con el anticuerpo monoclonal bevacizumab. Se muestra que la inmunización contribuye a normalizar los niveles de VEGF plaquetario y genera linfocitos T CD8+ citotóxicos. Se obtienen evidencias de la posibilidad de combinar el CIGB-247 con la quimioterapia. Conclusiones: Estos resultados permitieron el avance del CIGB-247 hacia los estudios clínicos fase II en combinación con otros regímenes onco-terapéuticos.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT  Introduction: Objectives: The primary aim of this work is to study the immunological effectors induced in CIGB-247-vaccinated patients. These effectors include humoral and cellular components of the immune system. Also, the goal of the present investigation is to detect different immunoglobulin classes and subclasses and its specificity for VEGF relevant epitopes, and demonstrate the induction of VEGF-specific and cytotoxic CD8 T lymphocytes. This research has, as an additional objective, the presentation of the first preliminary pieces of evidence of the feasibility to combine CIGB-247 with other anti-cancer treatments.  Methods: To investigate the vaccine-induced immunological effectors, ELISA and ELISPOT tests were used for monitoring the immune response elicited in cancer patients from the CENTAURO and CENTAURO-2 clinical trials and also those from the compassionate use program.  Results: Immunization with CIGB-247 elicited VEGF-specific IgM and IgA antibodies. Antibody response maturation was detected in some patients with long term overall survival, indicated by the subclass switching from IgG1 to IgG4. This antibody response blocked the interaction of VEGF with its receptors VEGFR2 and VEGFR1. This specific polyclonal antibody response inhibited the binding between VEGF and the monoclonal antibody bevacizumab, for that reason, it was directed to a relevant epitope on VEGF, implicated in the VEGF-induced proangiogenic activity. The vaccination contributed to normalizing platelet VEGF levels, and produced cytotoxic CD8 T lymphocytes. Some experimental evidence indicated the potential use of CIGB-247 in combination with chemotherapy. Conclusions: All these results allowed for the application of CIGB-247 in phase II clinical trials in combination with other cancer therapeutic treatments.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[VEGF]]></kwd>
<kwd lng="es"><![CDATA[CIGB-247]]></kwd>
<kwd lng="es"><![CDATA[inmunoterapia activa específica]]></kwd>
<kwd lng="es"><![CDATA[vacuna para cáncer]]></kwd>
<kwd lng="en"><![CDATA[VEGF]]></kwd>
<kwd lng="en"><![CDATA[CIGB-247]]></kwd>
<kwd lng="en"><![CDATA[specific active immunotherapy]]></kwd>
<kwd lng="en"><![CDATA[cancer vaccine]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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