This Phase II trial studies the overall tumor response of vaccine therapy in patientswith previously untreated Stage III or IV, asymptomatic, non-bulky follicular lymphoma. The vaccine contains an extract of the patient's own cancer cells and the immunostimulant protein, interleukin-2 (IL-2). It is hoped that when injected under the skin, the vaccine will enable the patient's immune system to recognize and destroy the cancer cells. The trial will also assess the safety of the vaccine, the time from vaccine treatment until the patient requires another type of anti-lymphoma treatment, progression-free survival, and the anti-tumor immune response.

This is a single-arm open-label pilot Phase II study. Following informed consent, eligible subjects will undergo excisional biopsy of a lymphoma-containing lymph node for diagnosis and for generation of the Oncoquest-L vaccine. Patients will receive subcutaneous injections consisting of their autologous tumor-derived Oncoquest-L vaccine starting at approximately 4 to 8 weeks after the biopsy. The first two doses will be given at a 2-week interval and the remaining 3 doses at monthly intervals. Patients will be monitored for response by performing imaging studies at baseline and 1 month after the fifth vaccination (Week 19). Additional imaging studies will be performed every 3 months for the first year and every 6 months during the second year until relapse or disease progression whichever occurs sooner.

Inclusion Criteria:

1. Follicular lymphoma (FL) grade 1, 2, or 3a diagnosed within 12 months of study enrollment

2. Age ≥ 18 years

3. Previously untreated Stage III or IV FL

4. A single peripheral lymph node of at least 1 x 1 cm in size accessible for excisional biopsy

5. Measurable or evaluable disease after obtaining tissue for vaccine production

6. Performance status (ECOG) of 0 or 1

7. Asymptomatic disease without B symptoms or severe pruritus

8. Low tumor burden as defined by the following criteria:

   • Normal lactic dehydrogenase
   • Largest tumor mass < 7 cm
   • Involvement of < 3 nodal sites with a diameter ≥ 3 cm
   • No clinically significant pleural effusion or ascites
   • Spleen size of ≤ 16 cm by CT scan
   • Circulating tumor cells < 5.0 x 109/L
   • No clinically significant organ compression

9. Adequate hematopoietic parameters:

   • Absolute neutrophil count ≥ 1.5 x 109/L
   • Platelet count ≥ 100 x 109/L
   • Hemoglobin ≥ 10 g/dL

10. Serum creatinine ≤ 2 x upper limit of normal (ULN)

11. Total bilirubin ≤ 2 x ULN unless considered secondary to Gilbert's syndrome. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase ≤ 2 x ULN

12. Fertile patients must use effective contraception during and for 12 months after completion of therapy

13. For fertile female patients, a negative pregnancy test result at enrollment

Exclusion Criteria:

1. Active HIV, hepatitis B, hepatitis C or other active infectious process
2. Pregnant or nursing women
3. Patients with previous history of malignancy within the past 2 years except curatively treated squamous or basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix.
4. Any medical or psychiatric condition that in the opinion of the principal investigator would compromise the patient's ability to tolerate this treatment
5. Concurrent treatment with immunosuppressive therapy