Centro De Inmunologia Molecular

Centro De Immunologia Molecular

Centro De Inmumologia Molecular

Kalet León Monzón

Tania Carmenate Portilla

Gertrudis Rojas Dorantes

Circe Mesa Pardillo

Luis Enrique Fernández Molina

Adriana Carr Perez

Maura Lisett Rábade Chediak

Diamile González Roche

Saumel Pérez Rodríguez

Yaima Tundidor Cabado

Rancés Blanco Santana

José Enrique Montero Casimiro

Saumel Pérez Rodriguez

Samuel Pérez Rodríguez

Amaury Pupo Meriño

Gabriel Márquez Perera

Amparo Emilia Macías Abraham

Giselle Hevia Hernández

Ángel De Jesús Corria Osorio

Agustin Bienvenido Lage Dávila

Tays Hernández García

Neris Michel Enamorado Escalona

Adys González Palomo

María Del Carmen Barroso Alvarez

Karina García Martínez

Augustín Bienvendo Lage Davila

The present invention relates to the field of Biotechnology, particularly to a method based on the introduction of a single mutation in the genes encoding the human IL-2 and the muteins derived thereof that results in increased secretion levels in different hosts without affecting their biological functions. In particular, these mutations are based on a non-conservative change in the amino acid located in position 35 in the primary sequence of human IL-2, preferably the substitutions are K35E, K35D and K35Q. Another object of the present invention are the expression systems used to obtain both the recombinant human IL-2 and the muteins derived thereof using the method described in this invention. The above-mentioned method is useful to improve the production efficiency of the recombinant human IL-2 and the muteins derived thereof both at laboratory and industrial scales. The proteins obtained using this method can be used for therapeutic purposes as well as in the in vitro expansion of T cells for adoptive transfer therapies.

Method for increasing the secretion levels of interleukin 2 and muteins thereof by introducing a point mutation

The present invention describes fusion proteins based on cytokines, called bi-cytokines (BC), specifically formed by the binding of an IL2 agonist mutein with a type I interferon (IFN), linked by an Fc region of a mutant human IgG1 and a connector peptide. The combination of an IL2 agonist mutein and a type I IFN in the structure of the bi-cytokines gives surprising immunoregulatory properties to these molecules and a superior therapeutic effect than that of parental cytokines, or their combination, which makes them attractive and novel molecules for the treatment of cancer. Pharmaceutical compositions comprising as an active ingredient the fusion proteins object of this patent are also described.

Fusion proteins composed of an interleukin-2 mutein and type I interferon

This invention provides new antibodies (Ab) and fragments that recognize the extracellular region of the human epidermal growth factor receptor (hEGFR) with a higher affinity than the Ab nimotuzumab, thus been able to recognize more efficiently lines with medium expression of EGFR. The present invention also relates to pharmaceutical compositions comprising as active principle the disclosed Abs and fragments and their use in the therapy of tumors with EGFR expression. In addition, it relates to the use of the Abs and fragments disclosed linked to a radioisotope or fluorophore for the localization of EGFR positive tumors. Additionally, the Abs and fragments disclosed can be used in the directionalization of the immune response to EGFR positive tumor cells when they are fused to protein or protein domains of immunological interest.

Antibodies with increased affinity for the epidermal growth factor receptor and fragments derived therefrom

The present invention relates to pharmaceutical compositions for the treatment of malignant tumors. Particularly those tumors that express EGFR and GM3 N-glycolyl ganglioside targets to enhance the therapeutic effect produced by separated therapies against these targets. The pharmaceutical compositions of the invention include antibodies and/or vaccines against each of the targets. Additionally the present invention relates to methods for applying the compositions of the invention.

Pharmaceutical compositions for the treatment of tumors expressing EGFR and GM3 N-glycolyl ganglioside (NeuGcGM3)

The present invention relates to the field of Biotechnology and more particularly to the mutated polypeptides of TGF&#x3b2; molecule whose primary sequence has a high homology with the sequence of human TGF&#x3b2;. These muteins lose their ability to interact with ALK5 but maintain their ability to interact with other receptors that are part of the receptor complex (T&#x3b2;RII and T&#x3b2;RIII). They have the property of antagonizing the signaling of all natural variants of TGF&#x3b2; ligands, dependent of ALK5 recruitment in the receptor complex, and have significant immunomodulatory effects. The present invention relates to pharmaceutical compositions comprising as active principle the polypeptides or fusion proteins disclosed and their use thereof given their modulating effect on the immune system in diseases such as cancer, diseases accompanied by fibrosis and chronic infectious diseases.

TGF&#x3b2;-derived polypeptides and uses thereof

The present invention relates to polypeptides which share primary sequence with human IL-2, except for several amino acids that have been mutated. The mutations introduced substantially reduce the ability of these polypeptides to stimulate in vitro and in vivo regulatory T cells (T CD4+CD25+FoxP3+) and make them more effective in the therapy of murine transplantable tumors. Also includes therapeutic uses of these mutated variants, used alone or in combination with vaccines for the therapy of diseases such as cancer or infections where the activity of regulatory T cells (Tregs) is relevant. In another aspect the present invention relates to pharmaceutical compositions comprising as active principle the polypeptides disclosed. Finally, the present invention relates to the therapeutic use of the polypeptides and pharmaceutical compositions disclosed due to their modulating effect of the immune system on diseases like cancer and chronic infectious diseases.

IL-2 derivative polypeptides

The present invention relates generally to polypeptides whose primary sequence has high sequence homology with human interleukin 2 (IL-2) with some punctual mutations in the sequence of native IL-2. The polypeptides of the present invention have an immunomodulatory effect on the immune system, which is selective/preferential on regulatory T cells. The present invention also relates to specific polypeptides whose amino acid sequence is disclosed herein. In another aspect the present invention relates to pharmaceutical compositions comprising as active ingredient the polypeptides disclosed. Finally, the present invention relates to the therapeutic use of the polypeptides and pharmaceutical compositions disclosed due to their immune modulating effect on diseases such as cancer and chronic infectious diseases.

Immunomodulatory interleukin-2 polypeptides and methods of treating melanoma

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Havana, Cuba

Kalet León Monzón