Efficacy of a Cancer Vaccine against <i>ALK</i>-Rearranged Lung Tumors

Voena, Claudia; Menotti, Matteo; Mastini, Cristina; Giacomo, Filomena Di; Longo, Dario Livio; Castella, Barbara; Merlo, Maria Elena Boggio; Ambrogio, Chiara; Wang, Qi; Minero, Valerio Giacomo; Poggio, Teresa; Martinengo, Cinzia; D’Amico, Lucia; Panizza, Elena; Mologni, Luca; Cavallo, Federica; Altruda, Fiorella; Butaney, Mohit; Capelletti, Marzia; Inghirami, Giorgio; Jänne, Pasi A.; Chiarle, Roberto

doi:10.1158/2326-6066.cir-15-0089

Cited by 48 publications

(51 citation statements)

References 48 publications

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“…In fact, these findings are consistent with the notably low immune infiltrating levels in ALK-rearranged NSCLC tumors [50], supportive of the notion that ALK-altered cancers can be immunosuppressive in their microenvironments. In line with these observations, Hong et al successfully demonstrated that anti-PD-1/PD-L1 antibodies could potentially be therapeutic in ALK-rearranged NSCLC [48].…”

Section: Alk Aberrations and Immune Evasion Signalingsupporting

confidence: 81%

“…In ALCL, combination of chemotherapy and ALK DNA vaccine could also prevent in vivo tumor growth and increased survival of lymphoma-bearing mice [61]. This ALK DNA vaccine also resulted in a 60% reduction in tumor number with survival doubling in ALK-positive NSCLC mouse models [50]. Another DNA plasmid-based ALK vaccine was also found to be effective in mounting specific anti-ALK immune response in ALK-positive NSCLC mouse models [62].…”

Section: Alk Neoantigens and Alk Vaccinesmentioning

confidence: 99%

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Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Wang

Lui

2020

Cancers

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Anaplastic lymphoma kinase (ALK) is mostly known for its oncogenic role in several human cancers. Recent evidences clearly indicate new roles of ALK and its genetic aberrations (e.g. gene rearrangements and mutations) in immune evasion, innate and cell-mediated immunity. New ALK-related immunotherapy approaches are demonstrating both preclinical and clinical promises. Here, we provide a timely review on the most updated laboratory and patient-related findings on ALK and immunity, which would grant us important insights for the development of novel ALK immunotherapies for ALK-altered cancers.

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Section: Alk Aberrations and Immune Evasion Signalingsupporting

confidence: 81%

Section: Alk Neoantigens and Alk Vaccinesmentioning

confidence: 99%

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Wang

Lui

2020

Cancers

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“…The immune targeting of tyrosine kinases is a promising alternative, or complement, to tyrosine kinase inhibitor-based targeted therapies [45,46]. When tyrosine kinases, such as ROS1, are expressed on the plasma membrane, their immune targeting can either be achieved via the passive administration of mAbs or by actively immunizing the patient against the tyrosine kinase.…”

Section: Of 23mentioning

confidence: 99%

Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

et al. 2020

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Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed with oncoantigen features, is activated by chromosomal rearrangement or overexpression in NSCLC and in several tumor histotypes. In this work, we have exploited transgenic mice harboring the activated K-Ras oncogene (K-RasG12D) that spontaneously develop metastatic NSCLC as a preclinical model to test the efficacy of ROS1 immune targeting. Indeed, qPCR and immunohistochemical analyses revealed ROS1 overexpression in the autochthonous primary tumors and extrathoracic metastases developed by K-RasG12D mice and in a derived transplantable cell line. As proof of concept, we have evaluated the effects of the intramuscular electroporation (electrovaccination) of plasmids coding for mouse- and human-ROS1 on the progression of these NSCLC models. A significant increase in survival was observed in ROS1-electrovaccinated mice challenged with the transplantable cell line. It is worth noting that tumors were completely rejected, and immune memory was achieved, albeit only in a few mice. Most importantly, ROS1 electrovaccination was also found to be effective in slowing the development of autochthonous NSCLC in K-RasG12D mice.

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“…High PD-L1 expression reduced ALK vaccine efficacy, which could be restored by administration of anti-PD-1 immunotherapy [101]. The hopes and concerns, about combination therapy with ALK-inhibitors and immunotherapy are pretty the same described with EGFR mutations, with a special interest in adverse events Ongoing but not recruiting [98] 10.…”

Section: Future Perspectives In Alk-rearranged Nsclcmentioning

confidence: 99%

Targeting EGFR and ALK in NSCLC: Current Evidence and Future Perspective

et al. 2016

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The advent of molecular therapy targeting specific driver oncogenes has dramatically changed the prognosis of a subset of NSCLC, dilating survival and improving the quality of life of patients with advanced disease. Two of the major targets for treatment with receptor TKIs are the activated mutated forms of the EGFR and the ALK gene fusions. In advanced NSCLC patients harboring EGFR mutations or ALK rearrangements, the use of TKIs in the firstline setting, have provided unexpected large progression-free survival and overall survival benefits, compared with cytotoxic chemotherapy. However, despite initial responses and durable remissions, the development of resistance inevitably leads to treatment failure. The aim of this review is to discuss the treatment strategy currently used for tumors harboring these two genetic targets and to focus on what will be available in clinical practice in the near future. KeywordsLung cancer is the leading cause of cancer-related deaths worldwide in both men and women, accounting for roughly 27% of all cancer-related deaths in 2015 [1]. Unfortunately, the prognosis of advanced (IIIB/IV) NSCLC remains poor with a 5-year survival rate of less than 17% [1]. Nevertheless, recent advances over the understanding of molecular mechanisms underling the development and progression of NSCLC revealed the presence of different targetable oncogenic drivers, thus identifying specific subsets of patients with distinct pathological and clinical features who might benefit from targeted therapies. This evidence paved the way to the era of personalized therapy, with EGFR and ALK target therapies representing the forefront of treatment of advanced NSCLC. EGFR mutations more frequently occur in patients with specific clinical features, such as never smoker, female gender, Asian ethnicity (30% of advanced NSCLCs as opposed to 15% for the Practice points• Despite recent improvements in diagnostic techniques and therapeutic approaches, the prognosis of advanced NSCLC remains dismal.• Molecular analyses (at least for EGFR, KRAS, ALK, ROS1) are mandatory in every patient diagnosed with NSCLC.

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Efficacy of a Cancer Vaccine against ALK-Rearranged Lung Tumors

Cited by 48 publications

References 48 publications

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

Targeting EGFR and ALK in NSCLC: Current Evidence and Future Perspective

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