Derivation of Tumor-specific Cytolytic T-Cell Clones from Two Lung Cancer Patients with Long Survival

Abstract

We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively. Autologous mixed lymphocyte-tumor cell cultures (MLTC) were produced with blood lymphocytes stimulated with irradiated autologous tumor cells. The first patient's SCLC cells, which carried a small amount of human leukocyte antigen (HLA) class I molecules, were incubated with interferon-gamma (IFN-gamma) before being used as stimulator cells. A cytolytic T-lymphocyte (CTL) clone was derived that specifically lysed the IFN-gamma-treated SCLC cells but did not lyse untreated tumor cells or autologous lymphoblasts. Clones of autologous tumor-specific CTL, directed against the NSCLC cells of the other patient, were also obtained. These tumor cells carried a higher level of HLA class I molecules and were lysed by the CTL without incubation with IFN-gamma. Altogether, these results indicate that SCLC and NSCLC cancer cells can be recognized by autologous CTL, and might therefore be susceptible to specific immunotherapy.

An HLA-Presented Fragment of Macrophage Migration Inhibitory Factor Is a Therapeutic Target for Invasive Breast Cancer

“…Several intracellular systems, including proteasomal degradation and the rapid processing of defective ribosomal products, provide HLA class I molecules with peptides derived from virtually all cellular functions and compartments (2,3). Indeed, a cornerstone of tumor immunology is recognition of cancer-specific, class I HLApresented peptides by CD8 + CTLs (4)(5)(6). Class I HLA-presented peptides distinguish the surface of cancerous cells and promote their recognition by the adaptive immune system.…”

From tumor antigens to immunotherapy

“…75 Using lung carcinoma cell lines, we and others have obtained autologous tumor-specific CTL and identified their target antigens. [76][77][78][79] The same types of antigens that were found on melanomas have now been identified on lung tumors. Two antigenic peptides presented by HLA-A24 molecules, expressed by 60% of the Japanese population, were reported to be shared tumor-specific antigens.…”

Induction of CD8 T-cell-Ifn-γ response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma

“…A clinically effective, cell-based vaccine furthermore requires that the tumor-specific antigens present in the vaccine cells are shared by the tumor of the patient. There is limited information available about shared antigens in NSCLC; 29,30 however, there is evidence for expression of identical tumor-associated antigens in melanomas [31][32][33][34] and other lung tumors. 23 Our study suggests that shared lung tumor antigens may be present and that they can be presented both by the direct and indirect antigen presentation pathway.…”