Background:
- Cancer-testis (CT) antigens (CTA), particularly those encoded by genes on the X
chromosome (CT-X antigens) have emerged as attractive targets for cancer
immunotherapy.
- Recent studies suggest that CT-X antigens which are up regulated by epigenetic
mechanisms may be preferentially expressed in pluripotent stem/tumor initiating
cells that mediate treatment resistance and metastasis of human cancers.
- Whereas pulmonary malignancies express a variety of CT-X antigens, immune responses
to these proteins are uncommon in lung cancer patients due to low-level,
heterogeneous antigen expression, epigenetic repression of genes regulating antigen
processing/presentation, and local as well as systemic immunosuppression in these
individuals.
- Conceivably, vaccination of lung cancer patients with tumor cells expressing high
levels of CT-X antigens in combination with regimens that inhibit immunosuppressive
functions of T regulatory cells and enhance activity of natural killer (NK) cells
will induce broad immunity to these antigens.
Primary Objectives:
- Phase I Component: To determine the safety of H1299 lung cancer cell lysate vaccines
administered with Montanide (Registered Trademark) ISA-51 VG adjuvant and N-803.
- Phase II Component: To assess the frequency of immunologic responses to purified
CT-X and autosomal CT antigens in NSCLC participants following vaccinations with
H1299 cancer cell lysate and Montanide (Registered Trademark) ISA-51 VG adjuvant in
combination with N-803.
Eligibility:
- Participants with pathologically confirmed Stage IB-IIIA (T2a-T4/N0, T1-T3N1,
T1-T2/N2) NSCLC per 8th edition TNM Staging System non-small cell lung cancer
(NSCLC) who have no clinical evidence of active disease (NED) following standard
therapy completed within the past 12 weeks.
- Participants must be 18 years or older with an ECOG performance status of 0-2.
- Participants must have adequate bone marrow, kidney, liver, lung, and cardiac
function.
- Participants receiving systemic immunosuppressive medications will be excluded.
- Participants with HIV will be excluded.
Design:
- Following recovery from surgery, and adjuvant therapy if indicated, eligible
participants will be vaccinated via deep subcutaneous (SQ) injection with H1299 cell
lysate and Montanide (Registered Trademark) ISA-51 VG (Trademark) adjuvant with or
without subcutaneous N-803 monthly until six vaccinations have been given.
- Imaging studies will be performed at baseline, one month following the 3rd and 6th
vaccinations, and at post-treatment follow-up (every 3 months for 3 years and then
every 6 months for another 2 years, for 5 years total follow-up).
- Leukapheresis will be performed at baseline and at treatment evaluation one month
following completion of the six vaccinations.
- Systemic toxicities and immunologic responses to therapy will be recorded.
- Pre- and post-vaccination serologic and cell mediated responses to a panel of CT-X
antigens will be assessed before and one month following completion of the six
vaccinations.
- Individuals deemed to have responded to vaccine treatment and exhibit no evidence of
disease recurrence or secondary malignancy will be eligible for 2 additional
vaccinations at 3 months after receiving the sixth vaccine and 6 months after
receiving the 6th vaccine with N-803.
- Numbers and percentages of immune subsets, soluble factors, and cytokines in
peripheral blood will be assessed before and after the six vaccinations.
- Immunologic responses to autologous tumor cells (if available) as well as pooled
lung cancer stem cell vs. normal lung-induced pluripotent stem cell (Lu-iPSC)
lysates will be evaluated in an exploratory manner.
- Up to 28 participants may receive study intervention on this protocol.