Immunotherapy for lung cancer

Therapeutic Vaccines

Therapeutic vaccines target shared or tumor-specific antigens, including MAGE-3, which is expressed in 42% of lung cancers, NY-ESO-1, which is expressed in 30% of lung cancers, p53, which is mutated in approximately 50% of lung cancers, survivin, and MUC1.



CRI/Ludwig investigators have shown promising results in lung cancer patients with vaccines targeting the NY-ESO-1 antigen. In a phase I clinical trial in Japan of a NY-ESO-1 vaccine completed in 2011, the treatment achieved integrated immune responses in nine of the ten patients treated, and two patients with lung cancer and one patient with esophageal cancer showed stable disease [5].

The slide at left shows expression of NY-ESO-1 in lung cancer, highlighted by antibody staining. Benign stromal cells and tumor infiltrating lymphocytes in between the clusters of tumor cells do not express NY-ESO-1. (Image courtesy of Yao-Tseng Chen.)

Therapeutic cancer vaccines in clinical trials for lung cancer include:
• GV1001, which targets the hTERT (human telomerase reverse transcriptase) subunit of telomerase, which is highly expressed in nearly all cancers but restricted in normal tissues, is being tested in a phase III study (NCT01579188) for patients with inoperable stage III NSCLC.
• Tergenpumatucel-L (HyperAcute®) for patients with stage III or IV NSCLC, currently being tested in a phase II/III trial (NCT01774578). Tergenpumatucel-L is a therapeutic vaccine consisting of human lung cancer cells genetically modified to include a mouse gene to which the immune system responds strongly.
• TG4010, which targets the MUC1 antigen, is being tested in a phase II/III study (NCT01383148) for patients with stage IV NSCLC.
• DRibbles (DPV-001), a vaccine made from nine cancer antigens plus TLR adjuvants, is being tested in a phase II trial for patients with stage III NSCLC (NCT01909752).
• MUC1 peptide-based vaccine for patients with any stage of NSCLC is currently being tested in a phase I/II trial (NCT01720836).
• CV9202 RNActive®-derived cancer vaccine, which consists of six different cancer antigens, is currently being tested in a phase I trial (NCT01915524) for patients with stage IV NSCLC.
• INGN, a dendritic cell-based vaccine targeting p53, is being tested in a phase II/III trial (NCT01383148) for patients with extensive stage SCLC.
• WT1 antigen vaccine is being tested in a phase II trial (NCT01265433) for patients with mesothelioma after completing surgery and chemotherapy and/or radiation.
• TroVax®, which targets the 5T4 protein widely found on mesothelioma cells, is being tested in a phase II trial for patients with mesothelioma (NCT01569919).

Adoptive T Cell Transfer

A third major avenue of immunotherapy for lung cancer is adoptive T cell transfer. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several clinical trials of adoptive T cell transfer techniques are currently under way.
• A phase II trial of T cells genetically engineered to recognize NY-ESO-1, given along with dendritic cells pulsed with NY-ESO-1 antigen as a vaccine, for patients with advanced or refractory malignancies, including lung cancer (NCT01697527).
• A phase II trial of tumor-infiltrating lymphocytes (TIL) in people with NSCL following chemotherapy (NCT02133196).
• A phase II trial of T cells engineered to target NY-ESO-1 antigen in patients with cancers that express NY-ESO-1, including lung cancer (NCT01967823).
• A phase I/II trial of T cells engineered to target VEGFR2 in patients with aggressive cancer that has not responded to standard therapy, including lung cancer (NCT01218867).
• A phase I//II trial of T cells engineered to target MAGE-A3 in patients with metastatic cancer that expresses MAGE-A3, including lung cancer (NCT02111850).
• A phase I/II trial of T cells genetically engineered to recognize mesothelin, for patients with mesothelin-expressing metastatic cancer or mesothelioma (NCT01583686).

Go to our Clinical Trial Finder to find clinical trials of immunotherapies for lung cancer that are currently enrolling patients.
- See more at: http://www.cancerresearch.org/ca ... thash.gLGnpLkV.dpuf