Inclusion Criteria:
* History of at least one of the following conditions in the previous 12 months:
* Colorectal adenoma(s) \>= 1 cm in maximal diameter
* Colorectal adenoma(s) with villous or tubulovillous histology
* Colorectal adenoma(s) with high grade (severe) dysplasia
* Presumptive evidence that all adenomatous lesions, including qualifying advanced adenoma, have been completely removed
* Ability to understand and the willingness to sign a written informed consent document
* Willingness to undergo screening tests and procedures
* Willingness to provide blood samples for toxicity monitoring and research purposes
* Not pregnant or nursing; note: a negative (serum or urine) pregnancy test must be documented =\< 7 days prior to registration/randomization for women of childbearing potential
* Willingness to employ adequate contraception through week 53 of the study; note: women of childbearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, abstinence) prior to study entry and for the period of active vaccination (through week 53); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her physician immediately
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
* Hemoglobin greater than 90% of the lower limit of institutional normal
* Platelets \>= 100 B/L (10\^9/L)
* White blood cell (WBC) \> 2.5 B/L (10\^9/L)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal
* Alkaline phosphatase =\< 1.5 x institutional upper limit of normal
* Total bilirubin =\< 1.5 x institutional upper limit of normal
* Blood urea nitrogen (BUN) =\< 1.5 x institutional upper limit of normal
* Creatinine =\< 1.5 x institutional upper limit of normal
* Antinuclear antibody (ANA) test result excludes overt autoimmune disease; note: test result may be reported in any of the following formats: =\< 1:160, negative, or \< 1.0
Exclusion Criteria:
* History of any colorectal cancer
* History of other malignancy =\< 5 years prior to the registration/randomization evaluation, with the exception of basal cell or squamous cell skin cancer
* Presence of an active acute or chronic infection or uncontrolled illness including, but not limited to unstable congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Acquired immunosuppressive diseases such as active human immunodeficiency virus (HIV) infection or congenital diseases of immunity
* History of heritable cancer syndrome (familial adenomatous polyposis \[FAP\], hereditary nonpolyposis colorectal cancer \[HNPCC\])
* History of auto-immune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, multiple sclerosis, Hashimoto's thyroiditis, or Grave's disease
* Current or planned use of immunomodulators including: infliximab, 6-MP (mercaptopurine), methotrexate, cyclosporine, or other immunomodulatory drugs
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent
* Pregnant women
* Breastfeeding women
* Diagnosis of nonalcoholic steatohepatitis (NASH) and a NAFLD (nonalcoholic fatty liver disease) activity score (NAS) \>= 5; NOTES and EXCEPTIONS: NAS is based on findings from a liver biopsy; participants with NAS of =\< 2 are eligible for enrollment; participants with NAS of 3-4 must be discussed with the principal investigator and Division of Cancer Prevention (DCP) before enrollment to consider other risk factors (i.e., obesity, alcohol intake); participants with a prior diagnosis of NASH and no available NAS must be discussed with the principal investigator and DCP before enrollment to considered risk factors (i.e., obesity, alcohol intake)
* Receiving any other investigational agent =\< 3 months prior to registration/randomization, except innocuous agents with no known interaction with the study agent (e.g., standard dose multivitamins or topical agents for limited skin conditions)
* Any use of oral corticosteroids =\< 12 weeks prior to registration/randomization
