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3. Long-term antigen-specific immune response by an oncolytic adenovirus encoding SP-SA-E7-4-1BBL in HPV-16 cancer model.

Author

Martinez-Perez, Alejandra G., Garza-Morales, Rodolfo, Loera-Arias, Maria de J., Villa-Cedillo, Sheila A., Garcia-Garcia, Aracely, Rodriguez-Rocha, Humberto, Flores-Maldonado, Orlando E., Valdes, Jesus, Perez-Trujillo, Jose J., and Saucedo-Cardenas, Odila

Abstract

Background: To describe an oncolytic adenovirus (OAd) encoding SP-SA-E7-4-1BBL that is capable of inducing tumor regression in therapeutic assays. Herein, we tested whether the antitumor effect is given by the induction of a tumor-specific immune response, as well as the minimum dose needed to elicit antitumor protection and monitor the OAd biodistribution over time. Methods and results: C57BL/6 mice (n = 5) per group were immunized twice with OAds encoding SP-SA-E7-4-1BBL, SA-E7-4-1BBL, or SP-SA-4-1BBL and challenged with TC-1 cancer cells. The DNA construct SP-SA-E7-4-1BBL was employed as a control via biolistic or PBS injection. Groups without tumor development at 47 days were rechallenged with TC-1 cells, and follow-up lasted until day 90. The minimum dose of OAd to induce the antitumor effect was established by immunization using serial dilution doses. The cytometry bead assay and the ELISpot assay were used to evaluate cytokine release in response to ex vivo antigenic stimulation. The distribution profile of the OAd vaccine was evaluated in the different organs by histological, immunohistochemical and qPCR analyses. The OAd SP-SA-E7-4-1BBL-immunized mice did not develop tumors even in a rechallenge. A protective antitumor effect was observed from a dose that is one hundredth of most reports of adenoviral vaccines. Immunization with OAd increases Interferon-gamma-producing cells in response to antigen stimulation. OAd was detected in tumors over time, with significant morphological changes, contrary to nontumor tissues. Conclusions: The OAd SP-SA-E7-4-1BBL vaccine confers a prophylactic, safe, long-lasting, and antigen-dependent antitumor effect mediated by a Th1 antitumor immune response. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Oncolytic Adenovirus Armed with a Novel Agonist of the CD137 Immune Checkpoint Stimulator Suppresses Tumor Growth.

Author

Ramos-Gonzalez, Martin R., Tarique, Mohammad, Batra, Lalit, Arguc, Feyza, Garza-Morales, Rodolfo, Shirwan, Haval, Yolcu, Esma S., and Gomez-Gutierrez, Jorge G.

Subjects
IMMUNE checkpoint proteins, TUMOR growth, KILLER cells, IMMUNE checkpoint inhibitors, ADENOVIRUSES, ADENOVIRUS diseases
Abstract

Natural 4-1BBL (CD137L) is a cell membrane-bound protein critical to the expansion, effector function, and survival of CD8+ T cells. We reported the generation of an active soluble oligomeric construct, SA-4-1BBL, with demonstrated immunoprevention and immunotherapeutic efficacy in various mouse tumor models. Herein, we developed an oncolytic adenovirus (OAd) for the delivery and expression of SA-4-1BBL (OAdSA-4-1BBL) into solid tumors for immunotherapy. SA-4-1BBL protein expressed by this construct produced T-cell proliferation in vitro. OAdSA-4-1BBL decreased cell viability in two mouse lung cancer cell lines, TC-1 and CMT64, but not in the non-cancerous lung MM14.Lu cell line. OAdSA-4-1BBL induced programmed cell death types I and II (apoptosis and autophagy, respectively), and autophagy-mediated adenosine triphosphate (ATP) release was also detected. Intratumoral injection of OAdSA-4-1BBL efficiently expressed the SA-4-1BBL protein in the tumors, resulting in significant tumor suppression in a syngeneic subcutaneous TC-1 mouse lung cancer model. Tumor suppression was associated with a higher frequency of dendritic cells and an increased infiltration of cytotoxic CD8+ T and NK cells into the tumors. Our data suggest that OAdSA-4-1BBL may present an efficacious alternative therapeutic strategy against lung cancer as a standalone construct or in combination with other immunotherapeutic modalities, such as immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Enhanced antitumor activity induced by a DNA vaccine encoding E7 antigen fused to an ERAD-targeting sequence

Author

Martínez-Puente, David Hernán, primary, Garza-Morales, Rodolfo, additional, Pérez-Trujillo, José Juan, additional, Bernabé-Acosta, Federico, additional, Villanueva-Olivo, Arnulfo, additional, García-García, Aracely, additional, Zavala-Flores, Laura Mireya, additional, Rodríguez-Rocha, Humberto, additional, Valdés, Jesús, additional, Saucedo-Cárdenas, Odila, additional, Montes de Oca-Luna, Roberto, additional, and Loera-Arias, María de Jesús, additional

Published
2022
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13. Enhanced antitumor activity induced by a DNA vaccine encoding E7 antigen fused to an ERAD-targeting sequence.

Author

Martínez-Puente, David Hernán, Garza-Morales, Rodolfo, Pérez-Trujillo, José Juan, Bernabé-Acosta, Federico, Villanueva-Olivo, Arnulfo, García-García, Aracely, Zavala-Flores, Laura Mireya, Rodríguez-Rocha, Humberto, Valdés, Jesús, Saucedo-Cárdenas, Odila, Montes de Oca-Luna, Roberto, and Loera-Arias, María de Jesús

Subjects
*DNA vaccines, *ANTINEOPLASTIC agents, *CHIMERIC proteins, *ANTIGENS, *AMINO acid sequence, *GENE targeting
Abstract

The endoplasmic reticulum (ER) is a key organelle in cell homeostasis and cell health through antigen presentation to immune cells. Thus, the ER has become a therapeutic target to induce cellular immune responses. We previously reported the antitumor effect of a DNA vaccine that expresses the E7 antigen fused to the cyclooxygenase-2 (COX-2) protein. This inflammation-related enzyme contains a degradation cassette associated with the endoplasmic reticulum-associated degradation (ERAD) pathway. To avoid the use of full-length COX-2 and any risk of adverse effects due to the activity of its catalytic site, we designed new versions of the fusion protein. These new constructs encode the E7 antigen fused to the signal peptide and the ERAD sequence of COX-2 with or without the membrane-binding domain (MBD) as well as deletion of the catalytic site. We evaluated the antigen-specific antitumor effect of these DNA constructs in murine prophylactic and therapeutic cancer models. These assays showed that the ERAD cassette is the minimum sequence in the COX-2 protein that induces an antitumor effect when fused to the E7 antigen with the advantage of eliminating any potential adverse effects from the use of full-length COX-2. [ABSTRACT FROM AUTHOR]

Published
2023
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18. Targeting E7 antigen to the endoplasmic reticulum degradation pathway promotes a potent therapeutic antitumor effect

Author

Martínez-Puente, David Hernán, primary, Garza-Morales, Rodolfo, additional, Pérez-Trujillo, José Juan, additional, García-García, Aracely, additional, Villanueva-Olivo, Arnulfo, additional, Rodríguez-Rocha, Humberto, additional, Zavala-Flores, Laura Mireya, additional, Saucedo-Cárdenas, Odila, additional, Montes de Oca-Luna, Roberto, additional, and Loera-Arias, María de Jesús, additional

Published
2021
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20. An Oncolytic Adenovirus Encoding SA-4-1BBL Adjuvant Fused to HPV-16 E7 Antigen Produces a Specific Antitumor Effect in a Cancer Mouse Model

Author

Martinez-Perez, Alejandra G., primary, Perez-Trujillo, Jose J., additional, Garza-Morales, Rodolfo, additional, Ramirez-Avila, Norma E., additional, Loera-Arias, Maria J., additional, Gomez-Gutierrez, Jorge G., additional, Saucedo-Cardenas, Odila, additional, Garcia-Garcia, Aracely, additional, Rodriguez-Rocha, Humberto, additional, and Montes-de-Oca-Luna, Roberto, additional

Published
2021
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22. Correction: Long-term antigen-specific immune response by an oncolytic adenovirus encoding SP-SA-E7-4-1BBL in HPV-16 cancer model.

Author

Martinez-Perez, Alejandra G., Garza-Morales, Rodolfo, de Loera-Arias, Maria J., Villa-Cedillo, Sheila A., Garcia-Garcia, Aracely, Rodriguez-Rocha, Humberto, Flores-Maldonado, Orlando E., Valdes, Jesus, Perez-Trujillo, Jose J., and Saucedo-Cardenas, Odila

Abstract

This document is a correction notice for an article titled "Long-term antigen-specific immune response by an oncolytic adenovirus encoding SP-SA-E7-4-1BBL in HPV-16 cancer model" published in Molecular Biology Reports. The correction states that the author Odila Saucedo-Cardenas should have been denoted as a corresponding author. The original article has been corrected accordingly. The document also includes contact information for the authors and their affiliations. [Extracted from the article]

Published
2024
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24. A DNA Vaccine Encoding SA-4-1BBL Fused to HPV-16 E7 Antigen Has Prophylactic and Therapeutic Efficacy in a Cervical Cancer Mouse Model

Author

Garza-Morales, Rodolfo, primary, Perez-Trujillo, Jose, additional, Martinez-Jaramillo, Elvis, additional, Saucedo-Cardenas, Odila, additional, Loera-Arias, Maria, additional, Garcia-Garcia, Aracely, additional, Rodriguez-Rocha, Humberto, additional, Yolcu, Esma, additional, Shirwan, Haval, additional, Gomez-Gutierrez, Jorge, additional, and Montes-de-Oca-Luna, Roberto, additional

Published
2019
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25. Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro

Author

Garza Morales, Rodolfo, González Ramos, Roxana, Chiba, Akiko, Montes de Oca Luna, Roberto, McNally, Lacey R., McMasters, Kelly M., Gomez Gutierrez, Jorge G, Garza Morales, Rodolfo, González Ramos, Roxana, Chiba, Akiko, Montes de Oca Luna, Roberto, McNally, Lacey R., McMasters, Kelly M., and Gomez Gutierrez, Jorge G

Abstract

Triple-negative breast cancer (TNBC) is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd)-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ)-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry) alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad) early region 1A (E1A) expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3)-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells.

Published
2018

27. Antitumor Response by Endoplasmic Reticulum-Targeting DNA Vaccine Is Improved by Adding a KDEL Retention Signal

Author

Pérez-Trujillo, José J., primary, Robles-Rodríguez, Olivia A., additional, Garza-Morales, Rodolfo, additional, García-García, Aracely, additional, Rodríguez-Rocha, Humberto, additional, Villanueva-Olivo, Arnulfo, additional, Segoviano-Ramírez, Juan C., additional, Esparza-González, Sandra C., additional, Saucedo-Cárdenas, Odila, additional, Montes-de-Oca-Luna, Roberto, additional, and Loera-Arias, María J., additional

Published
2018
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30. Adenovirus Lacking E1b Efficiently Induces Cytopathic Effect in HPV-16-Positive Murine Cancer Cells via Virus Replication and Apoptosis

Author

Martinez-Jaramillo, Elvis, primary, Garza-Morales, Rodolfo, additional, Wechman, Stephen L., additional, Montes de Oca-Luna, Roberto, additional, Saucedo-Cardenas, Odila, additional, Shirwan, Haval, additional, Yolcu, Esma, additional, McMasters, Kelly M., additional, and Gomez-Gutierrez, Jorge G., additional

Published
2018
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31. DNA vaccine encoding human papillomavirus antigens flanked by a signal peptide and a KDEL sequence induces a potent therapeutic antitumor effect

Author

Perez-Trujillo, Jose J., primary, Garza-Morales, Rodolfo, additional, Barron-Cantu, Jose A., additional, Figueroa-Parra, Gabriel, additional, Garcia-Garcia, Aracely, additional, Rodriguez-Rocha, Humberto, additional, Garcia-Juarez, Jaime, additional, Muñoz-Maldonado, Gerardo E., additional, Saucedo-Cardenas, Odila, additional, Montes-De-Oca-Luna, Roberto, additional, and Loera-Arias, Maria De Jesus, additional

Published
2017
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32. Vacunas terapéuticas contra el VPH: envío de antígenos al retículo endoplásmico

Author

Pérez Trujillo, José Juan, Figueroa Parra, Gabriel, Garza Morales, Rodolfo, Rodríguez Rocha, Humberto, García García, Aracely, Saucedo Cárdenas, Odila, Montes de Oca Luna, Roberto, Loera Arias, María de Jesús, Pérez Trujillo, José Juan, Figueroa Parra, Gabriel, Garza Morales, Rodolfo, Rodríguez Rocha, Humberto, García García, Aracely, Saucedo Cárdenas, Odila, Montes de Oca Luna, Roberto, and Loera Arias, María de Jesús

Published
2016

33. Diseño teórico de un modelo credit scoring basado en el método holt-winters para instituciones de microfinanzas

Author

Banda, Humberto, Garza Morales, Rodolfo, Banda, Humberto, and Garza Morales, Rodolfo

Abstract

The micro nancial institutions must assessing the buying power of its potential customers when awarding them with credit. This work aims to design a model that allows MFIs to establish the ability to pay its customers. This article gives a brief review of studies using di erent techniques to build credit scoring models and proposes a system based on the Holt-Winters method model to analyze the risk in granting microloans from expected cash ows, with emphasis on seasonality cash ow present. It should be noted that while this is a single variable, its relevance is considered itself a model of credit scoring., Para uma instituição de micro- nanciamento para avaliar adequadamente a capacidade de pagamento de seus clientes potenciais, previamente a uma aprovação de crédito, a capacidade de pagamento de crédito tem de ser avaliada. O principal objetivo deste trabalho é desenvolver um modelo que permite que as IMFs estabelecer a capacidade de pagamento dos clientes potenciais e face uma breve revisão das principais técnicas utilizadas por diferentes autores para desenvolver modelos de scoring de crédito e um novo modelo baseado na Holt-Winters com modelos espaço estado se propõe a analisar o risco microcrédito associada ao pagamento, com base na uxos de caixa esperados com ênfase na sazonalidade dos uxos de caixa esperados. É pertinente salientar que apesar de lidar com uma única variável, sua relevância é tal que ele é considerado um modelo de credit scoring por si só., Las instituciones de micro nanzas (IMF) deben valorar de manera adecuada la capacidad de pago que tienen sus clientes potenciales al momento de otorgarles un crédito. Este trabajo tiene como objetivo diseñar un modelo que permita a las IMF establecer la capacidad de pago de sus clientes y hace una breve revisión de trabajos que utilizaron diferentes técnicas para construir modelos de credit scoring, al tiempo que propone un modelo basado en el método Holt-Winters para analizar el riesgo en la concesión de microcréditos a partir de ujos de efectivo esperados, haciendo énfasis en la estacionalidad que dichos ujos presentan. Cabe señalar que si bien se trata de una única variable, por su relevancia se considera en sí misma un modelo de credit scoring.

Published
2015

36. Aplicación teórica del método Holt-Winters al problema de Credit Scoring

Author

Banda Ortiz, Humberto, Garza Morales, Rodolfo, Banda Ortiz, Humberto, and Garza Morales, Rodolfo

Abstract

El incremento de las instituciones de microfinanzas (imf) en México ha agudizado la competencia entre estas instituciones para aumentar su participación de mercado. No obstante las imf deben de valorar de manera adecuada el otorgamiento de créditos a sus clientes potenciales. Que los posibles clientes puedan pagar o no sus créditos depende directamente de los flujos de efectivo que generen por sus operaciones. En este trabajo se hace una revisión de la literatura de los trabajos más relevantes sobre los diferentes modelos de credit scoring y se propone una metodología teórica para analizar el riesgo de crédito en la concesión de microcréditos a partir de los flujos de efectivo esperados haciendo énfasis en la estacionalidad que dichos flujos presentan. Para ello se emplea el método Holt-Winters de pronóstico no lineal, con el fin de predecir el riesgo de que un cliente pague un préstamo (credit scoring).

Published
2014

38. Measurable order and simulation

Author

Garza-Morales, Rodolfo, GonzÁ¡lez-HernÁ¡ndez, Juan, and Villarreal-Rodríguez, César Emilio

Abstract

In this article is proposed a method for simulating random objects in a sample space Ω provided with a probability measure, a total order  and general conditions, such as the fact that for all ω0∈ Ω the set {ω ∈ Ω: ω  ω0} is measurable, the order topology relative to  is first countable, and a completion of Ω relative to the order is also first countable.

Published
2016
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