Immunotargeting of the xCT Cystine/Glutamate Antiporter Potentiates the Efficacy of HER2-Targeted Immunotherapies in Breast Cancer.

Cancer Immunology Research
Laura ContiFederica Cavallo

Abstract

Despite HER2-targeted therapies improving the outcome of HER2+ breast cancer, many patients experience resistance and metastatic progression. Cancer stem cells (CSC) play a role in this resistance and progression, thus combining HER2 targeting with CSC inhibition could improve the management of HER2+ breast cancer. The cystine-glutamate antiporter, xCT, is overexpressed in mammary CSCs and is crucial for their redox balance, self-renewal, and resistance to therapies, representing a potential target for breast cancer immunotherapy. We developed a combined immunotherapy targeting HER2 and xCT using the Bovine Herpes virus-4 vector, a safe vaccine that can confer immunogenicity to tumor antigens. Mammary cancer-prone BALB-neuT mice, transgenic for rat Her2, were immunized with the single or combined vaccines. Anti-HER2 vaccination slowed primary tumor growth, whereas anti-xCT vaccination primarily prevented metastasis formation. The combination of the two vaccines exerted a complementary effect by mediating the induction of cytotoxic T cells and of HER2 and xCT antibodies that induce antibody-dependent cell-mediated cytotoxicity and hinder cancer cell proliferation. Antibodies targeting xCT, but not those targeting HER2, directly ...Continue Reading

References

Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S RoveroG Forni
Feb 19, 2002·Journal of Virological Methods·Gaetano DonofrioVicky L van Santen
Jul 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sreenivasulu ChintalaRichard T Swank
Sep 8, 2005·The Journal of Biological Chemistry·Hideyo SatoShiro Bannai
Nov 23, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simona RollaFrancesco Ria
Jul 21, 2007·Reproduction : the Official Journal of the Society for the Study of Fertility·Gaetano DonofrioIain Martin Sheldon
Jan 3, 2008·Cancer Cell·Yves HüsemannChristoph A Klein
Aug 3, 2010·Antioxidants & Redox Signaling·Sanjay K GargRuma Banerjee
Jan 12, 2011·Expert Opinion on Drug Safety·Victoria LinaresJosé L Domingo
Sep 29, 2011·The Cancer Journal·Cecilia Larocca, Jeffrey Schlom
Feb 13, 2013·European Journal of Immunology·Frank J WardRobert N Barker
Jun 7, 2013·Cancer Research·Hasan Korkaya, Max S Wicha
Aug 24, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laura ContiFederica Cavallo
Jan 1, 2011·Cancers·Elena QuaglinoFederica Cavallo
May 3, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marco MacagnoFederica Cavallo
Aug 20, 2014·BioMed Research International·Laura ContiStefania Lanzardo
May 12, 2015·The Journal of Clinical Investigation·Daniel L AbravanelLewis A Chodosh
Nov 7, 2016·Lancet·Ophira GinsburgLesong Conteh
Nov 21, 2016·Lancet·Nadia Harbeck, Michael Gnant
Dec 16, 2016·Nature·Kathryn L HarperJulio A Aguirre-Ghiso
Dec 16, 2016·Nature·Hedayatollah HosseiniChristoph A Klein
Jan 27, 2017·Oncoimmunology·Silvio BandiniFederica Cavallo
Dec 23, 2017·Nature Communications·Emmanuel DornierJim C Norman
Jun 28, 2018·Cancer Immunology, Immunotherapy : CII·Roberto RuiuLaura Conti
Mar 14, 2019·World Journal of Gastroenterology : WJG·Adérson Omar Mourão Cintra DamiãoFlávio de Castro Feitosa
Apr 26, 2019·Proceedings of the National Academy of Sciences of the United States of America·Michael D ArensmanChristina H Eng
Aug 7, 2019·Progress in Molecular Biology and Translational Science·Roberto RuiuLaura Conti
Oct 23, 2019·Signal Transduction and Targeted Therapy·Jiani Wang, Binghe Xu
Oct 31, 2019·Journal of Hematology & Oncology·E KrasniqiP Vici
Jan 15, 2020·Seminars in Immunology·Elena QuaglinoFederica Cavallo

❮ Previous
Next ❯

Citations

Oct 9, 2020·The International Journal of Biochemistry & Cell Biology·Elena QuaglinoLaura Conti
Dec 17, 2020·International Journal of Molecular Sciences·Antonino Di LorenzoLaura Conti
Feb 27, 2021·Journal of Nanobiotechnology·Saghi NooraeiGholamreza Ahmadian
Apr 3, 2021·Trends in Endocrinology and Metabolism : TEM·Miriam ButlerFrank N van Leeuwen
Apr 21, 2021·Neoplasia : an International Journal for Oncology Research·Shanwen ChenPengyuan Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Breast Cancer: Chemo-Resistance

Some cancers are difficult to treat and aggressive including the "triple-negative" breast cancer. This type of cancer is chemoresistant even before chemotherapy begins. Here are the latest discoveries chemo-resistance in breast cancer.