Vaccines

Cancer in general is a well understood disease that develops due to the complete or partial tolerance of immune cells against the tumor cells. The treatment modality of cancer had acquired a new look since the introduction of advanced cancer immunotherapy. Genetic markers also have become the new normal treatment modalities opted for diverse cancer types.

This article will highlight the basics and types of vaccines available for Small Cell Lung Cancer.


Vaccine – Source

Vaccines for Small Cell Lung Cancer

Cancer vaccines are designed to induce adoptive immunity through eliciting humoral response against cancer antigens. Different allogeneic substances which trigger antigenic response like DNA carrying vectors, proteins, peptides, whole or mimic tumor cells/substances are employed. These cancer vaccines function like a typical vaccine producing prolonged active memory and reinforce during every re-exposure.

Many of vaccine approaches to SCLC have not been effective, but novel strategies in vaccine therapy show promising outcomes. Grant et al., 1999 reported that SCLC patients exhibited longer survival after vaccinating with anti-idiotypic antibody BEC2 with adjuvant Bacillus Calmette-Guerin (BCG) which mimics the ganglioside GD3.

Intradermal immunization for a period of 10 weeks in patients after standard treatment with chemotherapy or radiation developed anti-BEC2 antibodies. One in three patients developed anti-GD3 antibodies. The relapse free survival rates for patients with ED stage was 11 months (median) and with LD, the rates were greater than 47 months (median). The overall survival rate of patients with follow-up vaccine therapy was higher than patients who had undergone only standard therapy.

After this positive breakthrough, the efficacy of the vaccine was tried in more patients but LD stages were not effective with insignificant PFS. A phase III study on adjuvant vaccination with Bec2/ Bacille Calmette – Guerin in 515 LD-SCLC patients who had undergone first line radiation or chemotherapy showed no positive outcome in terms of survival or quality of life. 

Fuc-GM1 is present in excess number in lung cancer cells. The presence of Fuc-GM1 can be easily detected by immunostaining the SCLC cells. The expression of Fuc-GM1 on the SCLC affected tissues of the lung and the serum containing the SCLC has made it possible to target for an immunotherapy.

The predominantly exhibited antigens on the external surface in most cancer cells are the carbohydrate antigens. The antigens such as GM2, GD2, GD3, and 9-O -acetyl GD3 and Fucosyl GM1 in association with the vaccines have expressed their functional properties as prime targets for immunotherapy during clinical trials. The distribution level of the antigens over the surface of the cancer cells and healthy normal cells of the tissues greatly assist in choosing the target of choice for immunotherapy.

Viruses induced immunotherapy 

Viral immunotherapy Source

Genetically engineered viruses or viral particles are employed to potentially infect the tumor clones to overexpress tumor antigens which trigger major immunologic events like T cell infiltration, IFN gamma signaling and up-regulation of the PD-L1.

Oncolytic virotherapy promotes intra-tumoral T-cell infiltration and improves anti-PD-1 immunotherapy. This therapy shows promising prognosis in clinical trials. Intratumoral administration of H103 (type 2 genetically engineered antioncogenic adenovirus wi cr45th overexpression of heat shock protein (HSP) in patients with solid tumors were reported to be safe and efficacious.

One subject in the trial had extensive lung tumor indicating that the vaccine has positive prognosis in SCLC and NSCLC. More phase II trials are warranted to prove the therapeutic efficacy of the vaccine.

Another Phase I clinical study with a replication competent Picorna virus, namely Seneca Valley Virus was administered in population with solid tumors including SCLC patients. The dosage levels were well tolerated up to 1011 vp/kg with high viral clearance ratio, high replication potential inside tumor clones and anti-tumoral efficacy.

Natural killer cells induced immunotherapy

Natural killer cells also play a vital role in the suppression of the activity of the tumor cells. The property of the NK cells to permeate into the tumor cells, showcases a good development in the cancer treatment modality.  

These NK cells have the natural potentiality to exhibit a peculiar kind of receptors called killer immunoglobulin-like receptor (KIR).

These receptors possess the property of transferring genetic material, inhibiting signals and stimulatory signals to the NK cells.  Although clinical trials for SCLC in natural killer cells has not been reported, Phase I trials in other cancers like gastric carcinoma, lymphoma and myeloma were encouraging.

Conclusion

The basics behind this condition have greatly contributed to the prime concept of developing immunotherapy.

Therefore, already being developed as a well-established segment of the cancer treatment, immunotherapy has proved out to be a definite upsurging modality through its positive prognosis.

Many of the trials conducted are in Phase I stage with wide treatment landscape for future treatment.

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